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Serotonin plays active role in the sexual preference of mice

March 25, 2011 by Deborah Braconnier

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(PhysOrg.com) -- In a recent study published in Nature by Yan Liu and Yun'ai Jiang at Beijing's National Institute of Biological Sciences, the connection between serotonin and sexual preference in mice is presented. Liu and Jiang caution however that these results come from a study in mice and there has been no connection to homosexuality in humans.
For this study, Liu and Kiang first bred mice whose brains were unable to respond to serotonin. These mice lacked the gene called Lmxb1 which is needed to produce serotonin.
When placed in a cage with both male and female mice, these mice showed no preference towards either sex. When given a choice, these male mice would attempt to mount both sexes around 80 percent of the time. In a normal mouse, results show the percentage of female mounting to be 60 - 80, while the mounting of another male mouse at around 20 percent.
When these same mice were placed in a cage with straw bedding rubbed with the scent of both male and female genitals, they spent little time sniffing either, though the preference seemed to be geared toward the male scent.
The researchers repeated the same experiments with mice having a different genetic fault in the gene Tph2. This gene is responsible for aiding in the production of serotonin. These mice were also just as likely to mount mice of both sexes and did not show a preference to the smells of either males or females.
In a final experiment, Liu and Kiang injected normal male mice with a chemical called pCPA which is designed to deplete serotonin levels. The results showed that within three days these normal mice showed the same results as those mice without serotonin.
The study concludes that serotonin signaling plays a major role in the male sexual preference of mice, showing for the first time a connection with a neurotransmitter in the brain and sexual preference. Liu and Kiang do reiterate that there is no connection, however, between the results shown in these mice to that of human sexual preference.
More information: Molecular regulation of sexual preference revealed by genetic studies of 5-HT in the brains of male mice, Yan Liu, Yun’ai Jiang, Yunxia Si, Ji-Young Kim, Zhou-Feng Chen & Yi Rao, Nature (2011) doi:10.1038/nature09822 , http://www.nature.com/nature/journal/vaop/ncurrent/full/nature09822.html
© 2010 PhysOrg.com

A common thread: No pain, no smell

March 25, 2011 by Deborah Braconnier

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(PhysOrg.com) -- In a recent study published in Nature by Jan Weiss and Frank Zufall of the University of Saarland, School of Medicine, a connection has been made between the inability to feel pain and anosmia - the inability to smell. The connection discovered involves the sodium ion channel called Nav1.7.
The researchers examined three people with a rare condition known as congenital analgesia. This condition leaves patients with the inability to feel pain. The researchers were already aware that the cause of this disorder is a lack of the sodium ion channel Nav1.7 in the dorsal root ganglion and ganglia of the autonomic nervous system, but they wanted to learn if patients also experienced any other sensory issues.
The three participants were able to see and hear as well as any other healthy individual, but when it came to the sense of smell, they were unable to distinguish the odors of vinegar, orange, mint, perfume, or coffee. The study had scents so strong that others with normal senses of smell were unable to tolerate it.
To determine if it was in fact the same ion channel responsible for the sense of smell, Weiss and his team examined tissue samples from the nose and olfactory system of normal people and this revealed the Nav1.7 channels in the neuron’s cell membranes.
Weiss bred a group of mice lacking the Nav1.7 ion in their olfactory neurons and witnessed the same results. Mice generally search out and react to certain scents, but these mice showed no interest. When a mother mouse was separated from her young, she was unable to locate and gather them together.
The connection between Nav1.7 and sensory systems also shows earlier evidence that taste may also be included. The idea that our main senses are in some way linked to pain can now be better explored.
Other implications of this study could result in the ability to eventually treat people who have lost their sense of smell. This study could also have implications on the required side effects listings on many popular painkillers. These particular sodium ion channels are what are targeted by many painkillers, and a new side effect of anosmia may need to be listed.
More information: Loss-of-function mutations in sodium channel Nav1.7 cause anosmia, Nature (2011) doi:10.1038/nature09975 , http://www.nature.com/nature/journal/vaop/ncurrent/full/nature09975.html
© 2010 PhysOrg.com

Research may lead to new treatments for Parkinson's disease and other neurological disorders

March 25, 2011

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A group of scientists at Marshall University is conducting research that may someday lead to new treatments for repair of the central nervous system.
Dr. Elmer M. Price, who heads the research team and is chairman of Marshall's Department of Biological Sciences, said his group has identified and analyzed unique adult animal stem cells that can turn into neurons.
Price said the neurons they found appear to have many of the qualities desired for cells being used in development of therapies for slowly progressing, degenerative conditions like Parkinson's disease, Huntington's disease and multiple sclerosis, and for damage due to stroke or spinal cord injury.
According to Price, what makes the discovery especially interesting is that the source of these neural stem cells is adult blood, a readily available and safe source. Unlike embryonic stem cells, which have a tendency to cause cancer when transplanted for therapy, adult stems like those identified in Price's lab are found in the bodies of all living animals and do not appear to be carcinogenic.
"Neural stem cells are usually found in specific regions of the brain, but our observation of neural-like stem cells in blood raises the potential that this may prove to be a source of cells for therapies aimed at neurological disorders," Price added.
So far, the group at Marshall has been able to isolate the unique neural cells from pig blood. Price said pigs are often used as models of human diseases due to their anatomical and physiological similarities to humans. In the future, his lab will work to isolate similar cells from human blood, paving the way for patients to perhaps one day be treated with stem cells derived from their own blood.
More information: The team's research was published in a recent issue of the Journal of Cellular Physiology.
Provided by Marshall University Research Corporation

Research offers clue to halt Huntington's disease

March 25, 2011

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(PhysOrg.com) -- Surprising findings from a study into the brains of transgenic mice carrying the Huntington's disease mutation could pave the way for treatments which delay the onset and progression of this devastating genetic disease.
Researchers at the Queensland Brain Institute (QBI) have found that the brains of mice with Huntington's disease nevertheless retain populations of the precursor and stem cells which can give rise to new neurons.
The potential for stimulating the production of new neurons in Huntington's disease patients thus remained high, according to Dr Tara Walker, the postdoctoral fellow who carried out the work in the laboratory of Professor Perry Bartlett.
“Combined with previous findings which show that environmental enrichment and antidepressant treatment delayed both the onset and progression of Huntington's disease in mice, these findings are encouraging,” she says.
Huntington's disease (HD) is a neurodegenerative disorder that results in progressive motor, cognitive and psychiatric deficits which eventually lead to death.
Currently, there is no known cure.
However, the research, published this week in PLoS ONE, holds out hope that retained cell populations in the brains of Huntington's disease patients could one day be manipulated to replace degenerating neurons.
“Now we know that the capacity to generate neurons is retained in animals in even advanced stages of Huntington's disease, further research will need to explore what stops this process from occurring,” Dr Walker says.
“This may not only allow the restoration of neurogenesis, but may also allow this process to be harnessed to repair other areas of neuronal cell loss.”
Provided by University of Queensland (news : web)

Noninvasive brain stimulation may improve swallowing after stroke

March 24, 2011

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Stroke patients who received electrical brain stimulation coupled with swallowing exercises showed greater improvement in swallowing ability than patients who did not receive this stimulation, according to a pilot study reported in Stroke: Journal of the American Heart Association.
Difficulty swallowing, known as dysphagia, is a common and serious stroke complication. It can lead to aspiration, when food or foreign matter accidentally enters the lungs causing pneumonia. Aspiration and aspiration pneumonia are common complications after stroke and can be deadly.
The non-invasive brain stimulation used in this study (Transcranial Direct Current Stimulation, or tDCS) uses a weak electrical current. It is transmitted via electrodes placed on the scalp, to increase activity in targeted areas of the brain. Researchers noted:
• Patients who received brain stimulation increased their ability to swallow by more than 2.5 points on a seven-point swallowing scale, compared to slightly more than one point among those who did not receive the treatment. This was statistically significant, so it was not likely due to chance.
• Overall, swallowing ability improved by at least two points in 86 percent of patients receiving stimulation, and in 43 percent of those who did not. While these percentages showed a trend toward improvement, they did not reach statistical significance, likely due to the small study size.
"Further studies are warranted to refine this promising intervention by exploring effects of stimulation parameters, frequency of stimulation, and timing of the intervention in improving swallowing functions in dysphagic-stroke patients," researchers noted.
The study comprised 14 patients recruited from the inpatient stroke center at Beth Israel Deaconess Medical Center in Boston. All patients had suffered an ischemic stroke within the previous one to seven days. Participants were randomized so that some received tDCS to the brain regions that control swallowing while others received "sham stimulation." Those receiving sham stimulation were prepped as if they are going to receive tDCS but did not.
Provided by American Heart Association (news : web)

Long-term methadone treatment can affect the brain

March 23, 2011

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Methadone has been used to treat heroin addicts for nearly 50 years. Yet we have surprisingly incomplete knowledge about possible harmful effects from prolonged use. New research from the Norwegian Institute of Public Health shows that methadone affects the brain and impairs the attention of experimental animals.
In general, opioids such as heroin and morphine are known to weaken intellectual functions such as learning, memory and attention.
"It is therefore tempting to assume that methadone has similar effects," says researcher Jannike M. Andersen at the NIPH's Division of Forensic Toxicology and Drug Abuse.
For ethical reasons, methadone cannot be tested in long-term studies of healthy volunteers. It is also difficult to draw reliable conclusions from studies with methadone patients, because these studies often encounter methodological problems. Therefore, animals were used in the research.
New study of methadone
In a new study, Andersen and colleagues treated rats daily with methadone for three weeks and studied the rats' attention. The researchers measured how long the rats examined a new object introduced into their cage. The results show that the treatment clearly reduced the attention of the animals. This was true both when the rats had methadone in the body and, more importantly - a day after the last treatment, when the methadone had been excreted.
"The fact that the attention is impaired even after the drug was no longer present in the body suggests that methadone causes changes in brain cells. We do not yet know exactly what the changes are and how long-lasting they will be" says Andersen.
Is the human brain affected too?
-Does this unwanted effect have significance for people who are treated with methadone over many years?
"A positive treatment outcome depends on the patient functioning well - both socially and intellectually. If methadone treatment also impairs intellectual functions in humans, it could have a negative effect on the treatment result.
"We must now follow up the results from the animal studies to see if attention problems persist and to learn more about the biological mechanisms involved. Only then can we say anything more about the translation value of our findings for humans," says Andersen.
Methadone is a synthetic opioid that has been used in the treatment of heroin addicts worldwide since the mid-1960s. In Norway, methadone treatment was introduced in the 1990s.
More information: Jannike M. Andersen, Christine F. Olaussen, Åse Ripel and Jørg Mørland. Long-term methadone treatment impairs novelty preference in rats both when present and absent in brain tissue. Pharmacology Biochemistry and Behavior, 2011, online publication.
Provided by Norwegian Institute of Public Health

Spinal cord processes information just like areas of the brain

March 22, 2011

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Patrick Stroman is the director of the Queen's University MRI Facility and is currently mapping the function and information processing of the spinal cord. Credit: Queen's University
Patrick Stroman's work mapping the function and information processing of the spinal cord could improve treatment for spinal cord injuries.
"Basic physiology books describe the spinal cord as a relay system, but it's part of the central nervous system and processes information just like parts of the brain do," explains Dr. Stroman, director of the Queen's MRI Facility and Canada Research Chair in Imaging Physics.
Dr. Stroman's research is directed at precisely mapping the areas above and below a spinal cord injury in order to better determine the precise nature of an injury and the effectiveness of subsequent treatment. When medical research has advanced to a point where clinicians are able to bridge an injury on a spinal cord, Dr. Stroman's spinal mapping technique will be key in accurately pinpointing the injury to be bridged.
The technique involves capturing multiple images of the spinal cord using a conventional MRI system. The image capturing is repeated every few seconds over several minutes. During the imaging temperature sensations on the skin are varied allowing areas of the spinal cord that respond to the temperature changes to be detected in the MRI.
During their research, Dr. Stroman's team was also surprised to discover that levels of attention impact information processing in the spinal cord. By examining the differences in spinal cord functioning in people who were either alert or distracted by a task they were able to see changes in the level of cord activity picked up by the MRI scanner.
"The effect of attention is one of the reasons that when you're playing sports and you get hurt, you often don't become aware of the injury until after the game when your attention and focus changes," says Dr. Stroman. "We already knew that a person's level of attention affects information processing in the brain, but this finding has made us aware that level of attention has to be properly controlled in research that aims to accurately map spinal cord function."
Dr. Stroman's spinal cord mapping research has important implications for those with spinal cord injuries who suffer from chronic pain. The research also applies to any conditions—including multiple sclerosis, fibromyalgia, or congenital conditions—where the function of the spinal cord is affected.
Provided by Queen's University (news : web)

Scientists crack molecular code regulating neuronal excitability

March 22, 2011

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A high-resolution 3D structure of SNX27 PDZ domain bound to GIRK C-terminal tail. Surface rendering of the electrostatic potential (blue corresponds to positive charges) of SNX27 PDZ and the six-amino acid-“zip code” it recognizes. The red circle shows the newly identified 2nd site pocket and negatively charged GIRK3 residue. Credit: Image: Courtesy of Bartosz Balana and Paul Slesinger, Salk Institute for Biological Studies
A key question in protein biochemistry is how proteins recognize "correct" interaction partners in a sea of cellular factors. Nowhere is that more critical to know than in the brain, where interactions governing channel protein activity can alter an organism's behavior. A team of biologists at the Salk Institute for Biological Studies has recently deciphered a molecular code that regulates availability of a brain channel that modulates neuronal excitability, a discovery that might aid efforts to treat drug addiction and mental disorders.
In the this week's Online Early Edition of the Proceedings of the National Academy of Sciences, Paul Slesinger, Ph.D., Associate Professor in the Clayton Foundation Laboratories for Peptide Biology, and colleagues detail how a regulatory factor called SNX27 distinguishes a brain channel protein called GIRK (short for G-protein-coupled inwardly rectifying potassium channels) from structurally similar proteins and then targets it for destruction.
That work extends the group's 2007 study showing that when SNX27 proteins capture GIRK channels, reducing the number of channels at their rightful destination, the cell membrane. "We were curious about what determined the selectivity of this interaction," says Slesinger. "We knew that SNX27 interacted with a structural motif found on GIRK channels but many channel proteins display a similar motif. We wanted to know what allowed SNX27 to specifically choose GIRK channels."
Knowing this is critical because of the connection of GIRK channels to substance abuse. Slesinger and others have shown that alcohol or club drugs linked to sexual assault (GHB) affects GIRK channel function in the brain. Loss-of-inhibition behaviors associated with abuse of these substances result from the fact that GIRK channels allow potassium ions to leak out of a stimulated neuron, thereby dampening a cell's excitability.
In the new study Slesinger's team confirmed that SNX27 resides in neurons, just below the membrane where active GIRK channels sit. Additional experiments using brain cells manipulated to express abnormally high SNX27 levels showed that cells were less responsive to drugs that activate channels, suggesting that SNX27 waylays membrane-bound GIRKs and blocks their function.
The fact that SNX27 displays a common protein-interaction signature called PDZ domain suggested how SNX27 grabs its partner: GIRKs contain a short, 4-residue sequence that binds to PDZ domains, a recognition motif Slesinger likens to a zip code. But channels similar to GIRKs, called IRKs, displayed an almost identical sequence but were impervious to destruction by SNX27. "We were puzzled by this similarity and swapped the 4-residue code in IRK with the corresponding sequence from GIRK," says Slesinger. Surprisingly, this IRK/GIRK hybrid did not bind SNX27, indicating that the IRK lacked other elements necessary for SNX27 recognition.

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Left images show localization of SNX27 (shown in green) and NeuN (shown in red) in the CA1 region of the hippocampus, the brain’s learning and memory center. Right image shows superimposition of magnified region. Credit: Image: Courtesy of Kalyn Stern and Paul Slesinger, Salk Institute for Biological Studies
To define these new elements, Slesinger consulted with a long-standing collaborator, Senyon Choe, Ph.D., professor in Salk's Structural Biology Laboratory. Choe is an expert on a technique known as X-ray crystallography, used to determine the three-dimensional structure of proteins. The team scrutinized crystallized forms of SNX27 wrapped around the GIRK binding motif to try to visualize where the proteins made contact.
"We observed a binding cleft in the SNX27 PDZ domain and a region that formed another pocket with a lot of positive charges," says Slesinger. "The GIRK fragment lying there had a negative charge upstream of the 4-residue "zip code". That suggested that this second site allowed a previously unknown electrostatic interaction between these two proteins." Therefore, SNX27 may recognize a 6-residue motif, like the "zip plus 4' code.
More swap experiments targeting the GIRK negatively charged region confirmed the hypothesis. Synthetic forms of GIRK lacking the region no longer bound to SNX27. By contrast, an artificial version of IRK engineered to contain the GIRK negative charges homed to SNX27.
Most significant were experiments conducted by Bartosz Balana, Ph.D., a postdoctoral fellow in the Slesinger lab and the study's first author. Balana measured currents from cells engineered to carry GIRK channels lacking the charged region and found that GIRK currents were no longer dampened by SNX27, while cells expressing IRK channels displaying the false GIRK "address" now responded to SNX27. "This functional assay pin-pointed residues that dictate SNX27 binding beyond the normal PDZ recognition sequence," says Bartosz. "This supports a two-site binding model and emphasizes that second site can overrule binding at the classical site."
An interesting corollary to GIRKs' involvement in drug-related behavior is that SNX27 levels reportedly increase in rodent models of addiction to stimulants like cocaine and methamphetamine. Selectively blocking this newly identified interaction between GIRK and SNX27 might thwart addiction. "Now we are able to better understand the role of these channels in responses to drugs of abuse. It is our hope that that this work will lead to new strategies to treat diseases such as alcoholism or even, diseases of excitability, such as epilepsy." says Slesinger.
Also contributing to the study were Kalyn Stern and Laia Bahima of the Slesinger Lab and Innokentiy Maslennikov, and Witek Kwiatkowski of Choe's Structural Biology Laboratory.
Provided by Salk Institute (news : web)

Self-administered light therapy may improve cognitive function after traumatic brain injury

March 17, 2011

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At-home, daily application of light therapy via light-emitting diodes (LEDs) placed on the forehead and scalp led to improvements in cognitive function and post-traumatic stress disorder in patients with a traumatic brain injury (TBI), according to a groundbreaking study published in Photomedicine and Laser Surgery.
Margaret Naeser, PhD, LAc, VA Boston Healthcare System, Boston University School of Medicine, and colleagues from Massachusetts General Hospital, and Harvard-MIT Division of Health Sciences and Technology, in Boston, and MedX Health Inc. (Mississauga, ON, Canada), report on the use of transcranial LED-based light therapy to treat two patients with longstanding traumatic brain injury (TBI). Each patient applied LEDs nightly and demonstrated substantial improvement in cognitive function, including improved memory, inhibition, and ability to sustain attention and focus. One patient was able to discontinue medical disability and return to full-time work. These cognitive gains decreased if the patients stopped treatment for a few weeks and returned when treatment was restarted. Both patients are continuing LED treatments in the home. The findings are presented in "Improved Cognitive Function After Transcranial, Light-Emitting Diode Treatments in Chronic, Traumatic Brain Injury: Two Case Reports."
Low-level light therapy using lasers or externally placed LEDs to deliver red and near-infrared (NIR) light energy has been shown in cell-based studies to improve cellular metabolism and to produce beneficial physiological effects. In acute stroke in humans, for example, transcranial NIR light therapy applied less than 24 hours post-stroke was associated with improved outcomes.
"The results of this study will provide a basis for future therapeutic use of phototherapy to improve recovery after injury and facilitate management of other CNS disorders. The development of novel therapies to restore function after neurologic injury, stroke, or disease is an increasingly important goal in medical research as a result of an increase in non-fatal traumatic wounds and the increasing prevalence of dementias and other degenerative disorders in our aging population," says Raymond J. Lanzafame, MD, MBA, Editor-in-Chief of the Journal.
More information: The article is available free online at www.liebertpub.com/pho
Provided by Mary Ann Liebert, Inc.

Prozac reorganizes brain plasticity

March 16, 2011

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Selective serotonin reuptake inhibitors (SSRI) such as Prozac are regularly used to treat severe anxiety and depression. They work by immediately increasing the amount of serotonin in the brain and by causing long term changes in brain function. However it can take weeks of treatment before a patient feels any effect and both beneficial effects and side effects can persist after treatment is stopped. New research published by BioMed Central's open access journal Molecular Brain investigates physiological changes within the brain that may be caused by SSRI treatment.
The hippocampus is an area of the brain involved in long term memory and spatial awareness, and is involved in symptoms afflicting people with Alzheimer's disease, such as loss of memory and disorientation. Neuronal cells in the hippocampus can change their activity and strength of connections throughout life, a process known as plasticity, which thought to be one of the ways new memories are formed. Altered plasticity is often associated with depression and stress.
Researchers from the Department of Pharmacology, Nippon Medical School, showed that chronic treatment of adult mice with fluoxetine (Prozac) caused changes to granule cells, one of the main types of neuronal cells inside the hippocampus, and to their connections with other neuronal cells. The granule cells appeared to undergo serotonin-dependent 'dematuration', which increased their activity and reversed adult-type plasticity into an immature state. These changes to the cell's plasticity were associated with increased anxiety and in alternating between periods of hyper or hypo activity.
Katsunori Kobayashi explained, "Some of the side effects associated with Prozac in humans, such as anxiety and behavioral switching patterns, may be due to excessive dematuration of granule cells in the hippocampus."
More information: Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine, Katsunori Kobayashi, Yumiko Ikeda and Hidenori Suzuki, Molecular Brain (in press).
Provided by BioMed Central (news : web)

Integrity of the brain's reward system is linked to relapse following treatment

March 15, 2011

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The brain reward system (BRS) is involved in developing/maintaining addictive disorders, as well as relapse. New findings show that alcohol dependent individuals -- both future abstainers and relapsers -- have significantly thinner cortices in the BRS and throughout the entire brain. Findings support the influence of neurobiological factors on relapse.
At least 60 percent of individuals treated for an alcohol use disorder will relapse, typically within six months of treatment Given that the brain reward system (BRS) is implicated in the development and maintenance of all forms of addictive disorders, this study compared thickness, surface area and volume of neocortical components of the BRS among three groups: light drinkers, alcohol-dependent (AD) individuals still abstinent after treatment, and those who relapsed. Findings support the influence of neurobiological factors on relapse.
Results will be published in the June 2011 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.
"The BRS is a collection of regions/structures in the frontal and temporal lobes, limbic system, basal ganglia and other subcortical structures that form a functional network that is involved in determining if a substance or experience is pleasurable or aversive to use – which includes alcohol, food and other substances," explained Timothy C. Durazzo, assistant adjunct professor in the department of radiology at the University of California San Francisco, and corresponding author for the study. "The BRS is also involved in how we behave in response to the pleasurable or unpleasurable substance or situation"
Durazzo described this network as not only involved in the experience of pleasure and aversion, but also in the regulation of mood, higher-level cognitive abilities such as problem-solving, reasoning, decision-making, planning and judgment, as well as impulse control. "Abnormal BRS biology may also play a major role in the development and persistence of all forms of addiction," he said.
"If the BRS is not healthy or properly developed, this could lead to problems in delaying gratification, keeping emotions from driving decisions, and perceiving rewards in small yet healthy day-to-day events," added Susan F. Tapert, acting chief of psychology at the VA San Diego Healthcare System as well as professor of psychiatry at the University of California, San Diego. "Brain abnormalities therefore could result in more frequent, intense, or harmful intake of alcohol or other intoxicating substances."
Durazzo and his colleagues used magnetic resonance imaging (MRI) to examine BRS components among 75 (71 men, 4 women) treatment-seeking AD individuals at one-week of abstinence and 43 (39 men, 4 women) controls. The AD participants were followed for 12 months after the baseline examination, and classified as abstainers (n=24, no alcohol consumption) and relapsers (n=51, any alcohol consumption).
"We wanted to determine if at the beginning of treatment there were structural differences in the cortex of those who were able to maintain sobriety for at least 12 months after treatment versus those who relapsed within 12 months of treatment," said Durazzo. "We found that … the AD individuals – both future abstainers and relapsers – had significantly thinner cortices in the BRS and throughout the entire brain. However, the relapsers showed lower surface area and volume in the BRS than abstainers and controls. Overall, our results also indicated that the relapsers showed the most substantial structural abnormalities in the BRS."
Another important finding, added Durazzo, was that in AD participants who ultimately relapsed, those with the greater volume and surface area in several regions of the BRS had a less severe relapse. "That is, the length of relapse was shorter and they consumed less alcohol during the relapse," he said.
Durazzo added that these findings suggest that individuals who demonstrate the greatest degree of neurobiological abnormalities in the BRS at the beginning of treatment may be most at risk for relapse. "Specifically, impairments in the normal function of the BRS are associated with compromised problem-solving, reasoning, decision-making, planning and judgment, mood and impulse control," he said. "This may interfere with the ability to deal with the stressors and demands of everyday life and leave individuals more vulnerable to relapse."
"These individuals may have fewer neural resources dedicated to the ability to refrain from doing unhealthy activities or from postponing rewards," said Tapert. "This smaller volume and surface could also indicate that there are fewer brain cells available for finding small, frequent rewards throughout the day, so that more impactful experiences such as intoxication are sought out in order to provide the individual with a feeling of reward."
Both Durazzo and Tapert noted that this field of research is in its beginning stages. "It seems that MRI-based neuroimaging research can assist in identifying abnormalities in brain biology that may serve as markers for increased risk of relapse," said Durazzo. "Current medications and psychosocial interventions for AUD are only modestly effective in promoting long-term abstinence. Neuroimaging techniques can promote a better understanding of the neurobiological factors associated with relapse."
"A variety of brain imaging findings are emerging that can be used to help predict which patients may need a longer alcoholism treatment inpatient stay, or more intensive aftercare, or a more carefully designed follow-up plan to help prevent relapse," said Tapert. "For example, individuals with a smaller size of some reward-related frontal brain areas may need external constraints to help them keep from returning to heavy drinking."
"A substantial amount of research has investigated the psychological, psychiatric, sociodemographic and behavioral factors associated with relapse following treatment, but how brain biology and function contribute to relapse is not well understood," said Durazzo. "This neuroimaging research indicates that further study of how brain biology and function contribute to relapse is necessary to develop more effective medications and behavioral treatments for addictive disorders."
Provided by Alcoholism: Clinical & Experimental Research

Researchers question whether genius might be a result of hormonal influences

March 11, 2011

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A longstanding debate as to whether genius is a byproduct of good genes or good environment has an upstart challenger that may take the discussion in an entirely new direction. University of Alberta researcher Marty Mrazik says being bright may be due to an excess level of a natural hormone.
Mrazik, a professor in the Faculty of Education's educational psychology department, and a colleague from Rider University in the U.S., have published a paper in Roeper Review linking giftedness (having an IQ score of 130 or higher) to prenatal exposure of higher levels of testosterone. Mrazik hypothesizes that, in the same way that physical and cognitive deficiencies can be developed in utero, so, too, could similar exposure to this naturally occurring chemical result in giftedness.
"There seems to be some evidence that excessive prenatal exposure to testosterone facilitates increased connections in the brain, especially in the right prefrontal cortex," said Mrazik. "That's why we see some intellectually gifted people with distinct personality characteristics that you don't see in the normal population."
Mrazik's notion came from observations made during clinical assessments of gifted individuals. He and his fellow researcher observed some specific traits among the subjects. This finding stimulated a conversation on the role of early development in setting the foundation for giftedness.
"It gave us some interesting ideas that there could be more to this notion of genius being predetermined from a biological perspective than maybe people gave it credit for," said Mrazik. "It seemed that the bulk of evidence from new technologies (such as Functional MRI scans) tell us that there's a little bit more going on than a genetic versus environmental interaction."
Based on their observations, the researchers made the hypothesis that this hormonal "glitch" in the in-utero neurobiological development means that gifted children are born with an affinity for certain areas such as the arts, math or science. Mrazik cautions that more research is needed to determine what exact processes may cause the development of the gifted brain.
He notes that more is known about what derails the brain's normal development, thus charting what makes gifted people gifted is very much a new frontier. Mrazik hopes that devices such as the Functional MRI scanner will give them a deeper understanding of the role of neurobiology in the development of the gifted brain.
"It's really hard to say what does put the brain in a pathway where it's going to be much more precocious," he said. "The next steps in this research lay in finding out what exact stimuli causes this atypical brain development."
Provided by University of Alberta (news : web)

Scientists describe new model for neurodegeneration

March 10, 2011

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This image shows C. elegans expressing flourescently labelled progranulin in the head and intestines. Credit: A.Kao/UCSF
A team of scientists at the University of California, San Francisco (UCSF) has developed a new model for how inherited genes contribute to a common but untreatable and incurable neurodegenerative disease. The disease, frontotemporal lobar degeneration, is the second most common cause of dementia before age 65, after Alzheimer's disease.
Based on experiments in worms and mice, the UCSF team's work explains in part why the brain deteriorates in frontotemporal lobar degeneration, which may have implications for the understanding of several neurodegenerative disorders, including Alzheimer's and Parkinson's, as well as different forms of cancer.
"If our findings hold up," said Aimee Kao, an assistant adjunct professor in the Department of Neurology at UCSF, "they may suggest a new way to think about how to treat neurodegenerative diseases." Kao is first author on the study, led by Cynthia Kenyon, PhD, a professor of biochemistry and biophysics at UCSF and director of UCSF's Larry L. Hillblom Center for the Biology of Aging.
Disease Caused By Loss of Neurons
Generally scientists have blamed the mental decline associated with neurodegenerative diseases on the loss of neurons associated with the accumulation of insoluble protein in the brain – sticky plaques that interfere with and ultimately kill the brain's neurons.
In frontotemporal lobar degeneration, this loss of neurons happens in the frontal lobe – the part of the brain involved in such higher mental functions as art appreciation and emotional empathy. People with this disease can suffer from progressive difficulties with language, undergo personality and behavioral changes, and usually die within a decade of diagnosis.
The new work suggests that the accumulation of insoluble protein may not be the only cause of cognitive decline in frontotemporal lobar degeneration. Another mechanism could involve how the body deals with injured neurons in the brain.
A significant percentage of patients with frontotemporal lobar degeneration have mutations in the gene that produces a protein called progranulin. Scientists have known that people with these genetic mutations produce too little progranulin protein, but up to now it was unclear what role this played in disease development.
Now the work of the UCSF team suggests that progranulin regulates the speed with which dying cells are cleared.
The Speed of Brain Cell Death
Cells in the brain – as in the rest of the human body – die through a process known as apoptosis, or programmed cell death. In a sense, apoptosis is the cellular equivalent of a controlled implosion.
Rather than explode a condemned building in a crowded city and scatter its dust and rubble across surrounding neighborhoods, implosions minimize the fallout. Likewise, apoptosis of neurons prevents them from exploding and damaging the surrounding brain tissue, instead withering them away in protective fashion.
In their paper, Kao, Kenyon and their colleagues show that progranulin normally slows the process of apoptosis. In its absence, however, apoptotic cells are cleared more quickly, probably by neighboring cells, which engulf them.
Using a sophisticated microscope, the UCSF team showed that mutations to the progranulin gene caused cells in the microscopic roundworm C.elegans that were undergoing this programmed cell death to be cleared in about half the time, as compared to normal worms. They also found something similar in engulfing cells called macrophages that were taken from mice. When these cells lacked progranulin, they engulfed other, dying cells even faster.
"In both worms and cultured macrophages," Kao said, "the absence of progranulin cause more rapid clearance of dying cells."
Based on these findings, the team hypothesized that lack of progranulin may affect the ability of cells to recover from an injury. When individual cells are injured, the damage may or may not be fatal. Given enough time, the damaged cell could recover. However, if local engulfing cells are over-eager to remove the damaged cell, the cell may have too little time to recover. If this scenario occurred in the brain, then over time, the cumulative cell loss could lead to neurodegenerative disease.
These findings also have implications in the treatment of cancer, since some aggressive forms of breast, brain and bladder cancer produce increased levels of progranulin.
"These cancers may be using progranulin as a sort of 'invisibility shield' to hide from the surveillance of the immune system," Kao said. "Thus, progranulin could represent a druggable target in both neurodegeneration and some forms of cancer."
The study was published online last week by the journal Proceedings of the National Academy of Sciences.
Provided by University of California, San Francisco (news : web)

Brain cell regrowth linked to benefits of exercise, sexual behaviors and reproductive issues

March 10, 2011

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Two studies published by an interdisciplinary team of Hong Kong researchers in the current special issue of Cell Transplantation (20:1), now freely available on-line, link the regrowth of key adult brain cells (neurogenesis) in two critical areas of the brain to both the benefits of exercise as a stress reducer and also to sexual behavior and reproductive issues. The two studies reviewing the causes and impacts of neurogenesis came out of a recent Pan Pacific Symposium on Stem Cell Research held in Taichung, Taiwan.
Until the 1960s, the idea that the adult brain could experience neural cell re-growth was not accepted; research over the next 30 years confirmed that adult brain cells could, and did, in fact, regenerate. Recent research has focused on the role of neurogenesis. Subsequent important findings promise to change not only therapeutic interventions, but our understanding of aging, sexual potency and psychiatric diseases as well.
"The discovery of neural stem cells in the adult brain was a spectacular event that revolutionized the traditional view that the central nervous system did not generate new neurons in adulthood," said corresponding author Dr. Kwok-Fai So of the University of Hong Kong in the People's Republic of China. "Our research is focused on questions about the function and physiological significance of neurogenesis and what factors promote or suppress neurogenesis."
Physical exercise may counteract stress by promoting neurogenesis
"The beneficial effects of running correlated with increased adult neurogenesis, which may provide a hint that newborn neurons could be involved in counteracting stress-related disorders," said Dr. So. "Research has shown that exercise can improve mood and cognition and has also demonstrated that a deficit in adult neurogenesis may result in depressive disorders. Our research is aimed at examining the relationship between exercise as a way of combating stress and the possibility that exercise may promote neurogenesis and that neurogenesis functions as the mechanism of benefit."
According to the researchers, one important adult brain area that is a 'neurogenic zone' is the hippocampus, an area involved in memory and emotional regulation. The role of new neurons in hippocampal functions "remains poorly defined," however, but they add that the effect of stress on the hippocampus is well known. Stress, especially depression and post-traumatic brain injury, have been shown to shrink the hippocampus. Recent research has shown that exercise has a link to enhancing hippocampal 'plasticity' and the regrowth of neurons – neurogenesis.
"Recent findings suggest that hippocampal neurogenesis plays a role in the beneficial effects of exercise in countering stress," they concluded.
Citation: Yau, S-K.; Lau, B. W-M.; So, K-F. Adult Hippocampal Neurogenesis: A Possible Way How Physical Exercise Counteracts Stress. Cell Transplantation 20(1):99-111; 2011.
Adult neurogenesis, reproduction and sexual behavior
According to the researchers, recent studies suggest adult neurogenesis in the brain's subventricular zone (SVZ), which lines the ventricles (cavities) of the brain that contain cerebrospinal fluid, plays a role in reproductive function and possibly in maternal behaviors, although the function of "SVZ neurogenesis is obscure." They suggest that emerging evidence points to reproductive action and sexual cues, such as pheromones (known to play an important role in reproductive function), may play a role in regulating neurogenesis in the olfactory system, where the sense of smell is located, and in the SVZ. The precise contribution of newborn neurons to sexual behavior is still "under debate," the researchers point out. They cite animal studies showing that neurogenesis plays a role in female mate selection and that suppressed neurogenesis has been associated with decreased sexual performance.
"The potential importance of neurogenesis in sexual behavior, sexual cues and reproductive function has provided new insights," said Dr. So. "These insights might provide a better understanding of sexual dysfunction, sexual disorders and normal sexual functioning."
"These reviews show that the process of neurogenesis has far-reaching implications, including a beneficial exercise-induced response to stress and some degree of involvement with sexual behavior and reproduction," said Prof. Shinn-Zong Lin, professor of neurosurgery at China University Medical Hospital, Taiwan and chair of the Pan Pacific Symposium on Stem Cell Research where this work was first presented. "The studies reinforce the importance of a naturally occurring process that, until recently, was believed to be impossible."
Citation: Lau, B. W-M.; Yau, S-Y.; So, K-F. Reproduction: A New Venue for Studying Function of Adult Neurogenesis? Cell Transplantation 20(1):21-35; 2011.
More information: http://www.ingentaconnect.com/content/cog/ct/
Provided by Cell Transplantation Center of Excellence for Aging and Brain Repair

Brain implant surgeries dramatically improve symptoms of debilitating condition

March 8, 2011

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Implanting electrodes into a pea-sized part of the brain can dramatically improve life for people with severe cervical dystonia – a rare but extremely debilitating condition that causes painful, twisting neck muscle spasms – according to the results of a pilot study led by Jill Ostrem, MD and Philip Starr, MD PhD at the University of California, San Francisco.
Today, people with cervical dystonia can be treated with medications or injections of botulinum toxin (e.g., Botox®), which interrupt signals from the brain that cause these spasms. However, those treatments do not provide adequate relief for all patients.
Over the last decade, doctors at UCSF and elsewhere have turned to a technique called deep brain stimulation to help people with debilitating dystonia. Also used to treat Parkinson's disease and the neurological disorder essential tremor, the technique is like putting a pacemaker inside a heart patient's chest – except that deep brain stimulation requires a neurosurgeon to implant electrodes inside the brain.
Scientists are not sure exactly why deep brain stimulation works. The electrodes deliver electric current to tiny parts of the brain, likely altering abnormal brain circuitry and alleviating symptoms by overriding the signals coming from those parts of the brain.
Traditionally doctors have treated cervical dystonia with deep brain stimulation by targeting a brain nucleus known as the "globus pallidus internus." Reporting this week in the journal Neurology, the UCSF team described the results of the first detailed clinical study looking at deep brain stimulation targeting a completely different part of the brain: the "subthalamic nucleus."
"This target is very widely used for Parkinson's disease but not widely used for dystonia," said Starr, a professor of neurological surgery at UCSF and senior author of the paper.
The study, led by Ostrem, an associate professor of neurology at UCSF, involved nine patients followed for one year after surgery. "Patients in this study had failed medical treatments, but with the surgery, they were able to improve their movements and quality of life – as well as overcome some of their disability and pain," said Ostrem.
Video analysis and standard measures of dystonia showed the surgeries lowered pain, reduced spasms and improved the overall quality of life without causing serious side effects.
The team is now planning to enroll more patients into a longer study following outcomes for three years post-surgery.
"Medications and botulinum toxin injections still remain the first line of treatment," Ostrem said, "but for those who are really still suffering, we think DBS using this new stimulation location offers another choice for them."
Provided by University of California, San Francisco (news : web)

Pain research may pave the way to understanding and controlling chronic pain

March 8, 2011 by Kathy Keatley Garvey

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(PhysOrg.com) -- Researchers at the University of California, Davis have discovered a "cross-talk" between two major biological pathways that involve pain -- research that may pave the way to new approaches to understanding and controlling chronic pain. And they did it with something old, new, practical and basic.
The newly published research reveals that analgesia mediated by inhibitors of the enzyme, soluble epoxide hydrolase (sEH), is dependent on a pain-mediating second messenger known as cyclic adenosinemonophosphate or cAMP.
“The interaction of many complex biological pathways is essential for the development of persistent pain, whether inflammatory or neuropathic,” said lead researcher Bora Inceoglou of the Bruce Hammock lab, UC Davis Department of Entomology. Inflammatory pain includes arthritis, and neuropathic pain is linked to diabetes and other diseases, and trauma.
“Pain is a major health concern and painkiller medications or analgesics do different things,” Inceoglu said. Painkilling medications may target the pain, but have side effects or lack a broad-spectrum efficacy.
The collaborative study, the work of scientists in the UC Davis Department of Entomology, UC Davis Cancer Research Center, UC Davis School of Medicine and the School of Veterinary Medicine, is published in the March 7th early edition of the Proceedings of the National Academy of Sciences (PNAS).
An estimated 9 percent or 30 million adults in the United States suffer from moderate to severe non-cancer related chronic pain, according to the American Pain Society.
The messenger, cAMP, relays responses and mediates the action of many biological processes, including inflammation, and cardiac and smooth muscle contraction.
The research, done on rodents and funded by the National Institutes of Health, confirmed earlier studies at UC Davis that showed stabilization of natural epoxy-fatty acids (EFAs) through inhibition of sEH reduces pain. “However, in the absence of an underlying painful state, inhibition of sEH is ineffective,” Inceoglu said.
"This permits normal pain responses that serve to protect us from tissue damage to remain intact, while alleviating debilitating pain,” said co-author and pain neurobiologist Steven Jinks, associate professor of anesthesiology and pain medicine, UC Davis School of Medicine.
“Another advantage of inhibition of sEH is that it does not impair motor skills in several tests, unlike other analgesics,” said graduate student researcher Karen Wagner of the Hammock lab research team.
While conducting the research, the scientists found something they weren't looking for. "To our surprise, we found that cAMP interacts with natural EFAs and regulates the analgesic or pain activity of sEH inhibitors," Inceoglu said.
“This demonstrates the power of using advance instrumental analysis techniques to better understand the molecular mechanism of biological effects," said Nils Helge Schebb, a postdoctoral researcher from the Hammock group who worked on the quantification of the oxylipins in this project. Schebb leaves UC Davis this week to accept a position as junior research group leader at the University of Veterinary Medicine, Hannover, Germany.
“This is like something old, something new, something practical and something basic, too,” said Hammock, a distinguished professor of entomology who holds a joint appointment with the UC Davis Cancer Research Center.
Old? The research, Hammock said, involves “an old class of drugs known as phosphodiesterase inhibitors that likely exert part of their action by increasing the levels of natural compounds in the body called EETs (epoxyeicosatrienoic acids). Rolipram, Viagra, Theophyline, and Ibudilast are all in the phosphodiesterase-inhibitor class.”
New? The Hammock lab previously reported that a new class of experimental drugs called soluble epoxide hydrolase inhibitors (sEHIs) stabilize and also increase EETs.
Practical and basic? “A practical application of this work demonstrated by Bora Inceoglu is that the combination of this old and new class of drugs are highly effective in controlling pain,” said Hammock, senior author of the paper. “Of course, the basic aspects of the work include new insights in how EETs, cyclic nucleotides and the enzymes that degrade them interact to regulate a variety of biological functions.”
Both the old and the new class of drugs are based on inhibiting enzymes which degrade potent natural chemical mediators.
Inceoglu, Hammock, Jinks, Schebb, and Wagner co-authored the paper with veterinary anesthesiologist Robert Brosnan, associate professor of surgical and radiological sciences, School of Veterinary Medicine; and Christophe Morisseau, Arzu Ulu, Christine Hegedus and Tristan Rose, Department of Entomology and the Cancer Research Center.
The Jinks lab played a major role in the earlier UC Davis studies that showed a stabilization of EFAs through inhibition of sHE reduces pain. The Hammock lab works closely with the Jinks lab.
The pain discovery would not have been possible without sophisticated mass spectrometry equipment which allowed the analysis of the vanishingly small amounts of natural compounds that control pain and inflammation in the body, the researchers agreed.
Hammock described the potential practical applications of these fundamental discoveries as exciting. “We all have both suffered pain and have friends with unrelenting chronic pain problems,” he said. “The possibility of combining members of an old class of drugs with our new sEHI and actually providing relief for pain is very exciting.”
From his time as a graduate student, Hammock and his laboratory have focused on xenobiotic metabolism and largely on esterases and epoxide hydrolases. Current projects involve examining the role of esterases in insecticide resistance and human metabolism of pyrethroids. His laboratory is exploiting inhibitors of epoxide hydrolases as drugs to treat diabetes, inflammation, ischemia, and cardiovascular disease.
More information: http://www.pnas.or … 108.abstract
Provided by UC Davis (news : web)

How sweet it is: Why your taste cells love sugar so much

March 7, 2011

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Some of the green cell nuclei in this taste bud contain the KATP sugar sensor, indicated in red. One of several sugar sensors recently shown by Monell scientists to be present in sweet-sensing taste cells, KATP may help regulate sensitivity to sweet taste under different nutritional conditions. Credit: Karen Yee, Monell Center
A new research study dramatically increases knowledge of how taste cells detect sugars, a key step in developing strategies to limit overconsumption. Scientists from the Monell Center and collaborators have discovered that taste cells have several additional sugar detectors other than the previously known sweet receptor.
"Detecting the sweetness of nutritive sugars is one of the most important tasks of our taste cells," said senior author Robert F. Margolskee, M.D., Ph.D., a molecular neurobiologist at Monell. "Many of us eat too much sugar and to help limit overconsumption, we need to better understand how a sweet taste cell 'knows' something is sweet."
Scientists have known for some time that the T1r2+T1r3 receptor is the primary mechanism that allows taste cells to detect many sweet compounds, including sugars such as glucose and sucrose and also artificial sweeteners, including saccharin and aspartame.
However, some aspects of sweet taste could not be explained by the T1r2+T1r3 receptor. For example, although the receptor contains two subunits that must join together for it to work properly, Margolskee's team had previously found that mice engineered to be missing the T1r3 subunit were still able to taste glucose and other sugars normally.
Knowing that sugar sensors in the intestine are important to how dietary sugars are detected and absorbed, and that metabolic sensors in the pancreas are key to regulating blood levels of glucose, the Monell scientists used advanced molecular and cellular techniques to see if these same sensors are also found in taste cells.
The results, published in the Proceedings of the National Academy of Sciences, indicate that several sugar sensors from intestine and pancreas also are present in exactly those same sweet-sensing taste cells that have the T1r2+T1r3 sweet receptor.
"The taste system continues to amaze me at how smart it is and how it serves to integrate taste sensation with digestive processes," said Margolskee.
The different sugar taste sensors may have varied roles. An intestinal glucose sensor also found to be located in the sweet-sensitive taste cells may provide an explanation for another mystery of sweet taste: why just a pinch of table salt tastes sweet or salt added to baked goods enhances sweet taste. Known as SGLT1, this sensor is a transporter that moves glucose into the sweet taste cell when sodium is present, thus triggering the cell to register sweetness.
In pancreas, the sugar sensor known as the KATP channel, monitors glucose levels and triggers insulin release when they rise. The authors speculate that KATP may function in sweet taste cells to modulate taste cell sensitivity to sugars according to metabolic needs. For example, this sensor may respond to hormonal signals from the gut or pancreas to make taste cells less responsive to sweets after we have just eaten a sugary piece of pecan pie and do not need additional energy.
"Sweet taste cells have turned out to be quite complex. The presence of the KATP channel suggests that taste cells may play a role in regulating our sensitivity to sweet taste under different nutritional conditions," said first author Karen K. Yee, Ph.D., a cellular physiologist at Monell. "This knowledge may someday help us understand how to limit overconsumption of sweet foods."
Future studies will focus on understanding the complex connections between taste cells and the digestive and endocrine systems.
Provided by Monell Chemical Senses Center (news : web)

Flipping a switch on neuron activity

March 7, 2011

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All our daily activities, from driving to work to solving a crossword puzzle, depend on signals carried along the body's vast network of neurons. Propagation of these signals is, in turn, dependent on myriad small molecules within nerve cells -- receptors, ion channels, and transmitters -- turning on and off in complex cascades. Until recently, the study of these molecules in real time has not been possible, but researchers at the University of California at Berkeley and the University of Munich have attached light-sensing modules to neuronal molecules, resulting in molecules that can be turned on and off with simple flashes of light.
"We get millisecond accuracy," says Joshua Levitz, a graduate student at Berkeley and first author of the study. According to Levitz, the "biggest advantage is that we can probe specific receptors in living organisms." Previous methods using pharmacological agents were much less specific, affecting every receptor in every cell. Now, investigators can select individual cells for activation by focusing light. And by attaching light-sensing modules to one class of molecules at a time, they can parse the contributions of individual classes to neuronal behavior.
Levitz will be presenting a system in which G-protein-coupled receptors, molecules that play key roles in transmitting signals within cells, can be selectively activated. He is planning to use the system to study the hippocampus, a region of the brain where memories are formed, stored and maintained. There may be clinical utility to the system as well, he points out. G-protein-coupled receptors are also critical for vision in the retina, and light-sensing versions could potentially be introduced into people with damaged retinas in order to restore sight.
More information: The presentation, "Design and Application of a Light-Activated Metabotropic Glutamate Receptor for Optical Control of Intracellular Signaling Pathways" will be presented at 8:30 a.m. on March 7, 2011 in Room 309 of the Baltimore Convention Center. ABSTRACT: http://tinyurl.com/4lf9dse
Provided by American Institute of Physics

Scientists probe the role of motor protein in hearing loss

March 6, 2011

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From grinding heavy metal to soothing ocean waves, the sounds we hear are all perceptible thanks to the vibrations felt by tiny molecular motors in the hair cells of the inner ear. Researchers at the University of Pennsylvania School of Medicine have now identified the mechanism by which a single amino acid change can disrupt the normal functioning of one of the critical components of that physiology -- a molecular motor protein called myo1c, which resides in the cochlea of the inner ear.
The mutation (called R156W), was first identified in an individual suffering from cochlear hearing loss, and it affects the way the myo1c protein interacts with proteins known as actin filaments, another crucial component of the sensory apparatus of the inner ear. This interaction is essential for normal hearing, and scientists have already traced other causes of hearing loss to previously known mutations that interrupt it.
Now Michael Greenberg and his colleagues at UPenn have examined the biochemical and mechanical properties of the mutant myosin protein. Comparing constructs of the normal, "wild-type" protein to the R156W mutant, they examined the two proteins' kinetics and motility and discovered the mutant has a reduced sensitivity to mechanical loads and a lower duty ratio, meaning it spends less time attached to actin filaments.
Though the cochlear cell myo1c defects are associated with hearing loss, how this mutation causes the disease is still a mystery. The exact molecular role of myo1c is hazy, although it has been linked to several important cellular processes including hearing and insulin stimulated glucose uptake within cells. Understanding the defects caused by the R156 mutation could help to solve the puzzle.
"R156 is a highly conserved residue throughout the myosin superfamily. The fact that mutation of this residue affects the myosin duty ratio and strain sensitivity may very well be applicable in other myosins as well. In the long term, we hope to gain greater insight into the mechanism of myosin strain sensitivity and its role in mechanotransduction," says Greenberg.
More information: Presentation today at Biophysical Society Meeting in Baltimore. The Presentation, "A HEARING-LOSS ASSOCIATED MYO1C MUTATION (R156W) DECREASES THE MYOSIN DUTY RATIO AND FORCE SENSITIVITY" is at 1:45 p.m. on Sunday, March 6, 2011 in Hall C of the Baltimore Convention Center. ABSTRACT: http://tinyurl.com/4llnmve
Provided by American Institute of Physics

if you say that is all one more time i'm going to throw a live beehive at your head.

Human stem cells transformed into key neurons lost in Alzheimer's

March 4, 2011

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Northwestern Medicine researchers for the first time have transformed a human embryonic stem cell into a critical type of neuron that dies early in Alzheimer's disease and is a major cause of memory loss.
This new ability to reprogram stem cells and grow a limitless supply of the human neurons will enable a rapid wave of drug testing for Alzheimer's disease, allow researchers to study why the neurons die and could potentially lead to transplanting the new neurons into people with Alzheimer's.
The paper will be published March 4 in the journal Stem Cells.
These critical neurons, called basal forebrain cholinergic neurons, help the hippocampus retrieve memories in the brain. In early Alzheimer's, the ability to retrieve memories is lost, not the memories themselves. There is a relatively small population of these neurons in the brain, and their loss has a swift and devastating effect on the ability to remember.
"Now that we have learned how to make these cells, we can study them in a tissue culture dish and figure out what we can do to prevent them from dying," said senior study author Jack Kessler, M.D., chair of neurology and the Davee Professor of Stem Cell Biology at Northwestern University Feinberg School of Medicine and a physician at Northwestern Memorial Hospital.
The lead author of the paper is Christopher Bissonnette, a former doctoral student in neurology who labored for six years in Kessler's lab to crack the genetic code of the stem cells to produce the neurons. His research was motivated by his grandfather's death from Alzheimer's.
"This technique to produce the neurons allows for an almost infinite number of these cells to be grown in labs, allowing other scientists the ability to study why this one population of cells selectively dies in Alzheimer's disease," Bissonnette said.
The ability to make the cells also means researchers can quickly test thousands of different drugs to see which ones may keep the cells alive when they are in a challenging environment. This rapid testing technique is called high-throughput screening.
Kessler and Bissonnette demonstrated the newly produced neurons work just like the originals. They transplanted the new neurons into the hippocampus of mice and showed the neurons functioned normally. The neurons produced axons, or connecting fibers, to the hippocampus and pumped out acetylcholine, a chemical needed by the hippocampus to retrieve memories from other parts of the brain.
Human skin cells transformed into stem cells and then neurons
In new, unpublished research, Northwestern Medicine scientists also have discovered a second novel way to make the neurons. They made human embryonic stem cells (called induced pluripotent stem cells) from human skin cells and then transformed these into the neurons.
Scientists made these stem cells and neurons from skin cells of three groups of people: Alzheimer's patients, healthy patients with no family history of Alzheimer's, and healthy patients with an increased likelihood of developing the disease due to a family history of Alzheimer's because of genetic mutations or unknown reasons.
"This gives us a new way to study diseased human Alzheimer's cells," Kessler said. "These are real people with real disease. That's why it's exciting."
Researcher motivated by his grandfather's Alzheimer's disease
Bissonnette's persistence in the face of often frustrating research was fueled by the childhood memory of watching his grandfather die from Alzheimer's.
"I watched the disease slowly and relentlessly destroy his memory and individuality, and I was powerless to help him," Bissonnette recalled. "That drove me to become a scientist. I wanted to discover new treatments to reverse the damage caused by Alzheimer's disease."
"My goal was to make human stem cells become new healthy replacement cells so that they could one day be transplanted into a patient's brain, helping their memory function again," he said.
Bissonnette had to grow and test millions of cells to figure out how to turn on the exact sequence of genes to transform the stem cell into the cholinergic neuron.
"A stem cell has the potential to become virtually any cell in the body, from a heart cell to a layer of skin," he explained. "Its development is caused by a cascade of things that slowly bump it into a final cell type."
But it wasn't enough just to develop the neurons. Bissonnette then had to learn how to stabilize them so they lived for at least 20 days in order to prove they were the correct cells.
"Since this was brand new research, people didn't know what kind of tissue culture mature human neurons would like to live in," he said. "Once we figured it out, they could live indefinitely."
Provided by Northwestern University (news : web)

Brain rhythm predicts real-time sleep stability, may lead to more precise sleep medications

March 3, 2011

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A new study finds that a brain rhythm considered the hallmark of wakefulness not only persists inconspicuously during sleep but also signifies an individual's vulnerability to disturbance by the outside world. In their report in the March 3 PLoS One, the team from the Massachusetts General Hospital (MGH) Division of Sleep Medicine uses computerized EEG signal processing to detect subtle fluctuations in the alpha rhythm during sleep and shows that greater alpha intensity is associated with increased sleep fragility. The findings could lead to more precise approaches to inducing and supporting sleep.
"We found that the alpha rhythm is not just a marker of the transition between sleep and wakefulness but carries rich information about sleep stability," says Scott McKinney, informatics manager at the MGH Sleep Lab and lead author of the study. "This suggests that sleep – rather than proceeding in discrete stages – actually moves along a continuum of depth. It also opens the door to real-time tracking of sleep states and creates the potential for sleep-induction systems that interface directly with the brain."
One of numerous neuroelectrical signals produced by the brain and detected by electroencephalography (EEG), the alpha rhythm was first discovered nearly a century ago. Typically generated when the brain is relaxed but awake, the alpha rhythm fades as consciousness recedes and seems to disappear when sleep begins. However, a mathematical technique called spectral analysis, which quantifies the elemental oscillations that make up complicated signals, reveals that fluctuations in the alpha rhythm persist during sleep at levels that cannot be detected by visual inspection of an EEG.
Since alpha activity is associated with both wakefulness and receptiveness to sensory signals, the researchers hypothesized that it also could indicate a sleeper's sensitivity to environmental stimuli. To test this hypothesis, they monitored EEG rhythms in 13 healthy volunteers who spent three nights in the MGH Sleep Lab. At frequent intervals through each night the volunteers were exposed to 10 seconds of typical background noises like traffic or a ringing telephone. The sounds were repeated at successively louder levels until the EEG reflected that sleep had been disturbed.
Spectral analysis of the EEG measurements revealed that the strength of the alpha signal predicted how easily volunteers could be disturbed at the moment the measurement was taken, with a more intense alpha signal associated with more delicate sleep. The predictive power of alpha activity persisted for up to four minutes after the initial measurement, and the association was seen during both stage 2 and stage 3 non-REM sleep but not during REM sleep.
"We've found a quantitative measure that discloses sleep's momentary fragility," McKinney explains. "This technology may someday allow the development of adaptive sleep-inducing agents that can be guided by real-time feedback from neural activity – a great enhancement over conventional sleep drugs that act like sledgehammers, inducing a blanket sedation throughout the brain for an entire night."
Jeffrey Ellenbogen, MD, chief of the MGH Division of Sleep Medicine and senior author of the PLoS One report adds, "This finding paves the way toward futuristic sleep treatments in which medication or other therapies are delivered moment-to-moment, only when needed, to protect sleep when the brain is most vulnerable but otherwise let natural brain rhythms run their course. Learning more about the mechanism behind this association between the alpha rhythm and sleep fragility should lead to an even greater understanding of the factors that maintain sleep's integrity in the face of noise and other nuisances."
Provided by Massachusetts General Hospital (news : web)

Researchers find new light-sensing mechanism in neurons

March 3, 2011

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This image shows blue-light sensing arousal neurons. Credit: UCI
A UC Irvine research team led by Todd C. Holmes has discovered a second form of phototransduction light sensing in cells that is derived from vitamin B2. This discovery may reveal new information about cellular processes controlled by light.
For more than 100 years, it had been believed that the phototransduction process was solely based on a chemical derived from vitamin A called retinal. Phototransduction is the conversion of light signals into electrical signals in photoreceptive neurons and underlies both image-forming and non-image-forming light sensing.
In discovering this new light-sensing phototransduction mechanism, the UCI scientists found that phototransduction can also be mediated by a protein called cryptochrome, which uses a B2 vitamin chemical derivative for light sensing. Cryptochromes are blue-light photoreceptors found in circadian and arousal neurons that regulate slow biochemical processes, but this is the first time they have been linked to rapid phototransduction.
Their work appears March 3 on online Express site for the journal Science.
"This is totally novel mechanism that does not depend on retinal," said Holmes, a professor of physiology & biophysics. "This discovery opens whole new technology opportunities for adapting light-sensing proteins to drive medically relevant cellular activities."
This basic science breakthrough – "which literally and figuratively came 'out of the blue,'" Holmes said – has implications in the fast-growing field of optogenetics. Optogenetics combines optical and genetic research techniques to probe neural circuits at the high speeds needed to understand brain information processing. In one area, it is being used to understand how treatments such as deep brain massage can aid people with neurodegenerative diseases.
Holmes' team found that cryptochrome mediates phototransduction directly in fruit fly circadian and arousal neurons in response to blue-light wavelengths. The researchers also found that they could genetically express cryptochrome in neurons that are not ordinarily electrically responsive to light to make them light responsive.
Provided by University of California - Irvine

Stem cell study could aid motor neurone disease research

March 1, 2011

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Scientists have discovered a new way to generate human motor nerve cells in a development that will help research into motor neurone disease.
A team from the Universities of Edinburgh, Cambridge and Cardiff has created a range of motor neurons – nerves cells that send messages from the brain and spine to other parts of the body – from human embryonic stem cells in the laboratory.
It is the first time that researchers have been able to generate a variety of human motor neurons, which differ in their make-up and display properties depending on where they are located in the spinal cord.
The research, published in the journal Nature Communications, could help scientists better understand motor neurone disease. The process will enable scientists to create different types of motor neurons and study why some are more vulnerable to disease than others.
Motor neurons control muscle activity such as speaking, walking, swallowing and breathing. However, in motor neurone disease – a progressive and ultimately fatal disorder – these cells break down leading to paralysis, difficulty speaking, breathing and swallowing.
Previously scientists had only been able to generate one particular kind of motor neuron, which they did by using retinoic acid, a vitamin A derivative.
In the latest study, scientists have found a way to generate a wider range of motor neurons using a new process without retinoic acid.
Professor Siddharthan Chandran, Director of the Euan MacDonald Centre for Motor Neurone Disease Research at the University of Edinburgh, said: "Motor neurons differ in their make-up, so understanding why some are more vulnerable than others to disease is important for developing treatment for this devastating condition."
Dr Rickie Patani, of the University of Cambridge, said: "Although motor neurons are often considered as a single group, they represent a diverse collection of neuronal subtypes. The ability to create a range of different motor neurons is a key step in understanding the basis of selective subtype vulnerability in conditions such as motor neuron disease and spinal muscular atrophy."
Provided by University of Edinburgh

Signaling path in brain may prevent that 'I'm full' message, scientists discover

March 1, 2011

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Researchers at UT Southwestern Medical Center have identified a signaling pathway in the brain that's sufficient to induce cellular leptin resistance, a problem that decreases the body's ability to "hear" that it is full and should stop eating.
"Leptin resistance is a significant factor, yet the mechanisms that underlie the problem remain unclear," said Dr. Joel Elmquist, professor of internal medicine and pharmacology at UT Southwestern and senior author of the study appearing in the March issue of Cell Metabolism. "The fact that this cellular pathway may be involved is a novel observation."
Leptin is a hormone released by fat cells that is known to indicate fullness, or satiety, in the brain. If the body is exposed to too much leptin, however, it will become resistant to the hormone. Once that occurs, the body can't "hear" the hormonal messages telling the body to stop eating and burn fat. Instead, a person remains hungry, craves sweets and stores more fat instead of burning it.
Leptin resistance also causes an increase in visceral, or belly, fat, which has been shown to predispose people to an increased risk of heart disease, diabetes and metabolic syndrome.
For the current study, the researchers induced leptin resistance in organotypic brain slices from mice. This research technique, used commonly in neuroscience, enabled the researchers to maintain the cellular and anatomical relationships and some of the network connections that normally exist within the brain.
"We're not dispersing cells. We're leaving them in a microenvironment that simulates what's going on in the brain," Dr. Elmquist said.
When the researchers began manipulating the network – known as cAMP-EPAC pathway – they found that activating this previously unexplored signaling avenue is enough to induce leptin resistance within hypothalamic neurons, a critical site of leptin action. They also found that when the pathway was blocked, the cells were no longer resistant to leptin.
"In the follow-up experiments, which we conducted in mice, we were able to induce leptin resistance simply by infusing activators of this pathway, further supporting our theory that this signaling pathway may contribute to leptin resistance in obesity," said Dr. Makoto Fukuda, instructor of internal medicine at UT Southwestern and the study's lead author.
Dr. Elmquist said that while the EPAC signaling pathway itself is not novel, this is the first time it has been studied in the hypothalamus and in the context of energy balance and leptin signaling.
The next step, Dr. Elmquist said, is to investigate how critical the EPAC pathway actually is in leptin responsive neurons and to determine its role in maintaining energy balance and leptin sensitivity.
"These results are potentially interesting and provocative, but the physiological importance remains to be seen," Dr. Elmquist said. "If, however, this pathway is indeed important, it will offer new insights into the mechanisms that high levels of leptin cause in leptin resistance."
Provided by UT Southwestern Medical Center (news : web)

Study shows acupressure effective in helping to treat traumatic brain injury

February 28, 2011

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Jin Shin acupressure treatment, an ancient form of medicine, has been shown by a CU-Boulder research team to be an effective complementary treatment for those suffering from mild traumatic brain injury. Credit: Photo by Casey A. Cass/University of Colorado
A new University of Colorado Boulder study indicates an ancient form of complementary medicine may be effective in helping to treat people with mild traumatic brain injury, a finding that may have implications for some U.S. war veterans returning home.
The study involved a treatment known as acupressure in which one's fingertips are used to stimulate particular points on a person's body -- points similar to those stimulated with needles in standard acupuncture treatments, said CU-Boulder Professor Theresa Hernandez, lead study author. The results indicate a link between the acupressure treatments and enhanced cognitive function in study subjects with mild traumatic brain injury, or TBI.
"We found that the study subjects with mild traumatic brain injury who were treated with acupressure showed improved cognitive function, scoring significantly better on tests of working memory when compared to the TBI subjects in the placebo control group," said Hernandez, a professor in CU-Boulder's psychology and neuroscience department. "This suggests to us that acupressure could be an effective adjunct therapy for those suffering from TBI."
The acupressure treatment type used in the study is called Jin Shin. For the study, Hernandez and her colleagues targeted the 26 points on the human body used in standard Jin Shin treatments ranging from the head to the feet. The study subjects all received treatments by trained Jin Shin practitioners.
According to practitioners, Jin Shin acupressure points are found along "meridians" running through the body that are associated with specific energy pathways. It is believed that each point is tied to the health of specific body organs, as well as the entire body and brain, Hernandez said.
"Think of the meridians as freeways and the pressure points as towns along the way," she said. "When there is a traffic jam in Denver that causes adverse effects as far away as Boulder, clearing the energy blocks, or in this case traffic jams, helps improve flow and overall health."
The study involved 38 study subjects, each of whom was randomly assigned to one of two groups -- an experimental group that received active acupressure treatments from trained experts and a control group that received treatments from the same experts on places on the body that are not considered to be acupressure points, acting as a placebo. The study was "blinded," meaning the researchers collecting data and the study participants themselves did not know who was in the experimental group or the placebo group until the end of the study.
The team used a standard battery of neuropsychological tests to assess the results. In one test known as the Digit Span Test, subjects were asked to repeat strings of numbers after hearing them, in both forward and backward order, to see how many digits they could recall. Those subjects receiving active acupressure treatments showed increased memory function, said Hernandez.
A second standard psychology test used for the study, called the Stroop Task, measured working memory and attention. The test subjects were shown the names of colors like blue, green or red on a computer screen. When the names of the particular colors are viewed on the screen in a different color of ink -- like the word "green" spelled out in blue ink -- test subjects take longer to name the ink color and the results are more error-prone, according to Hernandez.
The Stroop Test subjects in the CU-Boulder study wore special caps wired with electrodes to measure the brain activity tied to specific stimuli. The results showed those who received the active acupressure treatments responded to stimuli more rapidly than those who received the placebo treatments, Hernandez said.
"We were looking at synchronized neural activity in response to a stimulus, and our data suggest the brains of those in the active acupressure group responded differently when compared to those in the placebo acupressure group," she said.
A paper on the subject was published in the January issue of the Journal of Neurotrauma, a peer-reviewed publication on the latest advances in both clinical and laboratory investigations of traumatic brain and spinal cord injury. Co-authors on the study included CU-Boulder's Kristina McFadden, Kyle Healy, Miranda Dettman, Jesse Kaye and Associate Professor Tiffany Ito of psychology and neuroscience.
Funded by the Colorado Traumatic Brain Injury Trust Fund, the study is believed to be one of the first placebo-controlled studies ever published in a peer-reviewed medical journal showing the benefit of acupressure to treat patients with TBI, Hernandez said.
"We would like to see if the Jin Shin treatment is useful to military veterans returning home with traumatic brain injury, a signature wound prevalent in the wars in Iraq and Afghanistan," said Hernandez. The Jin Shin acupressure treatment can be taught to family and friends of those with TBI and can even be used as a self-treatment, which could allow for more independence, she said.
In a 2010 stroke study led by Hernandez, the researchers concluded that Jin Shin acupressure triggered a larger and faster relaxation response during active treatments and a decreased stress response following active treatments compared with what was seen in placebo treatments. Hernandez and her colleagues are embarking on a new study on the use of Jin Shin acupressure in athletes to see if the enhanced relaxation response and decreased stress seen in the stroke study can reduce the likelihood of athletic injury.
In 2002, Hernandez partnered with former Colorado Rep. Todd Saliman to initiate the Colorado Traumatic Brain Injury Trust Fund, a statute that has generated nearly $2 million to the state annually since 2004 from surcharges to traffic offenses like driving while impaired and speeding. Roughly 65 percent of the money goes toward rehabilitation and care services for individuals with TBI, about 30 percent goes for TBI research and 5 percent for TBI education. Because of the statute, nearly 4,000 Colorado citizens with TBI have received care and rehabilitation services for brain injuries.
Hernandez will be honored on March 3 in Denver by the Colorado Traumatic Brain Injury Program with the establishment of the annual Theresa D. Hernandez TBI Trust Fund Community Award, becoming its first recipient. Saliman also will be honored at the ceremony.
Provided by University of Colorado at Boulder (news : web)

Binge eaters' dopamine levels spike at sight, smell of food

February 28, 2011

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Brain scans comparing the effects of methylphenidate plus food stimulation to placebo plus neutral stimulation in obese binge eaters and obese control subjects who were not binge eaters. Since the radiotracer competes with the brain’s natural dopamine to bind to receptors, a weaker signal from the tracer (less red) indicates more dopamine in the brain. The decrease in red in the binge eaters exposed to food and methylphenidate (lower right) compared to the placebo/neutral stimulation condition (lower left) therefore indicates that food stimulation triggered a spike in dopamine levels in these subjects. There was no difference in dopamine levels between these conditions in the non-binge eaters (upper images).
(PhysOrg.com) -- A brain imaging study at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory reveals a subtle difference between ordinary obese subjects and those who compulsively overeat, or binge: In binge eaters but not ordinary obese subjects, the mere sight or smell of favorite foods triggers a spike in dopamine - a brain chemical linked to reward and motivation. The findings - published online on February 24, 2011, in the journal Obesity - suggest that this dopamine spike may play a role in triggering compulsive overeating.
"These results identify dopamine neurotransmission, which primes the brain to seek reward, as being of relevance to the neurobiology of binge eating disorder," said study lead author Gene-Jack Wang, a physician at Brookhaven Lab and the Mount Sinai School of Medicine. Previous studies conducted by Wang's team have identified a similar dopamine spike in drug-addicted individuals when they were shown images of people taking drugs, as well as other neurochemical similarities between drug addiction and obesity, including a role for dopamine in triggering desire for drugs and/or food.
"In earlier studies of normal-weight healthy people who had been food-deprived for 16 hours, we found that dopamine releases were significantly correlated with self-reports of hunger and desire for food. These results provided evidence of a conditioned-cue response to food," Wang said.
In the current study, the researchers suspected that binge-eating obese subjects would show stronger conditioned responses to food stimuli when compared with non-binging obese subjects.
"Understanding the neurobiological mechanisms underlying food stimulation might point us toward new ways to help individuals regulate their abnormal eating behaviors," Wang said.
The scientists studied 10 obese people with a clinical diagnosis of binge eating disorder, based on evaluations at St. Luke's-Roosevelt Hospital, and 8 obese subjects who were not binge eaters.
The scientists used positron emission tomography (PET) to scan the subjects' brains after injecting a radiotracer designed to bind to dopamine receptors in the brain. Because the tracer competes with the brain's natural dopamine to bind to these receptors, the signal picked up by the PET scanner provides an inverse measure of the brain's dopamine levels: a strong signal from the bound tracer indicates low levels of natural brain dopamine; a low signal from the tracer indicates high levels of dopamine in the brain.
Each subject was scanned four times on two different days to test the effects of food stimulation vs. neutral stimulation with and without pre-administration of a drug known to amplify dopamine signals. The drug, methylphenidate, blocks the reuptake of dopamine from brain synapses, allowing it to linger longer. In scans without methylphenidate, subjects were given a placebo drug.
In the food stimulation condition, research subjects' favorite foods were heated (if appropriate) and waved in front of their mouths and noses so they could smell and even taste tiny amounts swabbed onto their tongues. For the neutral stimulation scans, researchers displayed non-food-related pictures and inanimate objects such as toys and clothing items in close proximity so research subjects could smell them while lying in the scanner. In all cases, research subjects had been fasting for 16 hours prior to scans.
Results
Food stimulation with methylphenidate significantly increased dopamine levels in the caudate and putamen regions of the brain in binge eaters but not in the non-binge eaters. Subjects with the most severe binge eating disorder, as assessed by psychological evaluations, had the highest dopamine levels in the caudate.
Dopamine levels did not rise significantly in other brain regions or under any other condition (neutral stimulation with or without methylphenidate, or food stimulation without methylphenidate) in either group, and were not correlated with body mass index of the research subjects. Assessments of the levels of receptors for dopamine also did not differ between the two groups.
"So the key difference we found between binge eaters and non-binge eating obese subjects was a fairly subtle elevation of dopamine levels in the caudate in the binge eaters in response to food stimulation," Wang said.
"This dopamine response is in a different part of the brain from what we've observed in studies of drug addiction, which found dopamine spikes in the brain's reward center in response to drug-associated cues. The caudate, in contrast, is believed to be involved in reinforcement of action potentially leading to reward, but not in processing of the reward per se. That means this response effectively primes the brain to seek the reward, which is also observed in drug-addicted subjects," Wang said.
Inasmuch as binge eating is not exclusively found in obese individuals, the scientists believe further studies are warranted to assess the neurobiological factors that may differentiate obese and non-obese binge eaters.
More information: Scientific paper: "Enhanced Striatal Dopamine Release During Food Stimulation in Binge Eating Disorder": http://www.nature. … 201127a.html
Provided by Brookhaven National Laboratory (news : web)

Secretions of the mind

February 25, 2011

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Enhanced BDNF secretion by overexpression of CAPS2 (top), photographed at four-minute intervals, in hippocampal neurons from mice lacking the CAPS2 gene (bottom: without CAPS2 expression). Credit: The National Academy of Sciences of the United States of America
A molecule called calcium-dependent activator protein for secretion 2 (CAPS2) promotes the secretion of a neurotrophic factor that is critical for the proper development and survival of networks of interneurons in the brain’s hippocampus, researchers in Japan have shown.
Teiichi Furuichi of the RIKEN Brain Science Institute in Wako, and his colleagues showed previously that CAPS2 is involved in secretion of brain-derived neurotrophic factor (BDNF) from cerebellar granule cells and neurons in the cerebral cortex, but its exact role in secretion was unclear.
Yo Shinoda, a researcher of the Furuichi's group used antibody staining to examine the distribution of CAPS2 in cultured hippocampal neurons of mice. He saw that most CAPS2 localized along the axons, but found some on secretory vesicles that contain and release BDNF.
To investigate the role of CAPS2 in BDNF secretion, the researchers visualized BDNF secretion in cells from mutant mice lacking the CAPS2 gene. They found that these cells secreted significantly less BDNF than normal cells, but the level returned to normal or became enhanced when they transfected the cells with CAPS2 (Fig. 1).
The researchers then examined hippocampal interneurons in the mutant mice and compared them with those in normal animals. These interneurons synthesize and secrete γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain. The mutants had reduced numbers of these cells in hippocampus of the brain. Furthermore, analysis of inhibitory synapses under the electron microscope revealed that the mutants had fewer synaptic vesicles than the normal animals. The researchers also revealed that the vesicles were distributed over a smaller area within presynaptic boutons, the specialized area where loaded vesicles dock to release their contents.
Finally, the researchers used microelectrodes to examine the electrical activity of the cells from the mutants and discovered that there was a significant reduction in both the number and size of spontaneous inhibitory postsynaptic currents. Consequently, the mutant mice displayed anxiety-like behaviors that would be expected with a GABA signaling impairment.
The findings show that CAPS2 promotes BDNF secretion by affecting the kinetics of its release from dense-core vesicles, and that BDNF is essential for proper development and function of the networks of inhibitory interneurons in the hippocampus, the researchers conclude. “We are interested in the molecular mechanism underlying the enhanced BDNF secretion, and would like to analyze the kinetics of secretion using state-of-the art cell imaging technology,” Furuichi explains. “We also want to study relation of CAPS2-BDNF-GABA pathways in anxiety and depressive behavior.”
More information: Shinoda, Y., et al. Calcium-dependent activator protein for secretion 2 (CAPS2) promotes BDNF secretion and is critical for the development of GABAergic interneuron network. Proceedings of the National Academy of Sciences USA 108, 373–378 (2011). http://www.pnas.or … 108.abstract
Provided by RIKEN (news : web)

Cell phone use may have effect on brain activity, but health consequences unknown

February 22, 2011

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In a preliminary study, researchers found that 50-minute cell phone use was associated with increased brain glucose metabolism (a marker of brain activity) in the region closest to the phone antenna, but the finding is of unknown clinical significance, according to a study in the February 23 issue of JAMA.
"The dramatic worldwide increase in use of cellular telephones has prompted concerns regarding potential harmful effects of exposure to radiofrequency-modulated electromagnetic fields (RF-EMFs). Of particular concern has been the potential carcinogenic effects from the RF-EMF emissions of cell phones. However, epidemiologic studies of the association between cell phone use and prevalence of brain tumors have been inconsistent (some, but not all, studies showed increased risk), and the issue remains unresolved," according to background information in the article. The authors add that studies performed in humans to investigate the effects of RF-EMF exposures from cell phones have yielded variable results, highlighting the need for studies to document whether RF-EMFs from cell phone use affects brain function in humans.
Nora D. Volkow, M.D., of the National Institutes of Health, Bethesda, Md., and colleagues conducted a study to assess if cell phone exposure affected regional activity in the human brain. The randomized study, conducted between January 1 and December 31, 2009, included 47 participants. Cell phones were placed on the left and right ears and brain imaging was performed with positron emission tomography (PET) with (18F)fluorodeoxyglucose injection, used to measure brain glucose metabolism twice, once with the right cell phone activated (sound muted) for 50 minutes ("on" condition) and once with both cell phones deactivated ("off" condition). Analysis was conducted to verify the association of metabolism and estimated amplitude of radiofrequency-modulated electromagnetic waves emitted by the cell phone. The PET scans were compared to assess the effect of cell phone use on brain glucose metabolism.
The researchers found that whole-brain metabolism did not differ between the on and off conditions. However, there were significant regional effects. Metabolism in the brain region closest to the antenna (orbitofrontal cortex and temporal pole) was significantly higher (approximately 7 percent) for cell phone on than for cell phone off conditions. "The increases were significantly correlated with the estimated electromagnetic field amplitudes both for absolute metabolism and normalized metabolism," the authors write. "This indicates that the regions expected to have the greater absorption of RF-EMFs from the cell phone exposure were the ones that showed the larger increases in glucose metabolism."
"These results provide evidence that the human brain is sensitive to the effects of RF-EMFs from acute cell phone exposures," the researchers write. They add that the mechanisms by which RF-EMFs could affect brain glucose metabolism are unclear.
"Concern has been raised by the possibility that RF-EMFs emitted by cell phones may induce brain cancer. … Results of this study provide evidence that acute cell phone exposure affects brain metabolic activity. However, these results provide no information as to their relevance regarding potential carcinogenic effects (or lack of such effects) from chronic cell phone use."
"Further studies are needed to assess if these effects could have potential long-term harmful consequences," the authors conclude.
The results of this study add information about the possible effects of radiofrequency emissions from wireless phones on brain activity, write Henry Lai, Ph.D., of the University of Washington, Seattle, and Lennart Hardell, M.D., Ph.D., of University Hospital, Orebro, Sweden, in an accompanying editorial.
"Although the biological significance, if any, of increased glucose metabolism from acute cell phone exposure is unknown, the results warrant further investigation. An important question is whether glucose metabolism in the brain would be chronically increased from regular use of a wireless phone with higher radiofrequency energy than those used in the current study. Potential acute and chronic health effects need to be clarified. Much has to be done to further investigate and understand these effects."
The editorial authors also question whether the findings of Volkow et al may be a marker of other alterations in brain function from radiofrequency emissions, such as neurotransmitter and neurochemical activities? "If so, this might have effects on other organs, leading to unwanted physiological responses. Further studies on biomarkers of functional brain changes from exposure to radiofrequency radiation are definitely warranted."
More information: JAMA. 2011;305[8]808-814.
Provided by JAMA and Archives Journals (news : web)

'Round-the-clock' lifestyle can disrupt metabolism, brain and behavior

February 21, 2011

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Simple minded. Researchers found that disrupting the circadian cycles of mice led to changes in the top part of the complex dendritic tree of cortical neurons (above). These trees were less complex in animals thrown off their schedule.
(PhysOrg.com) -- In Civilization and Its Discontents, Sigmund Freud argued that modern society was hard on human psychology, forcing people to get along in unnaturally close quarters. Now newly published research from The Rockefeller University points out a different discontent in the developed world, namely, the disruption of our natural sleep cycles, thanks to the ubiquity of electric lighting. Experiments on mice, published this month in Proceedings of the National Academy of Sciences, found that throwing off their evolutionarily ancient circadian rhythms by artificially altering the length of their days has a substantial impact on the body and the brain. The work suggests that our modern round-the-clock lifestyle could disrupt metabolism, interfere with learning and impact behavior in ways that we’re just beginning to understand.
Researchers led by Ilia Karatsoreos, a postdoc in Bruce S. McEwen’s Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, housed mice for 10 weeks in 20-hour light-dark cycles, at odds with their natural 24-hour circadian cycle. They found that after six weeks, the disrupted mice got fatter, showed less mental flexibility and were more impulsive than mice kept on their natural schedule. The findings were originally presented at a Society for Neuroscience’s conference in 2009.
Looking ahead, Karatsoreos says, a main goal is to understand how this environmental disruption works at the biochemical level. “We are interested in how the light cycle changes affects ‘clock genes’ — the actual molecular gears of the circadian clock within cells — in different brain regions, particularly the prefrontal cortex, and how this translates to changes in the functioning of the cells in that region.”
At the same time, the researchers are working to understand the changes at the cellular and molecular level of peripheral tissues, especially those involved in metabolism and energy usage, such as the liver and the adipose tissues.
“The circadian system is a ‘web,’ with rhythms at the molecular level driving rhythms at the cellular level, which results in rhythms at the tissue level,” Karatsoreos says. “This can lead to a cascading set of effects throughout the whole organism, and we want to understand how exactly that happens.”
The researchers believe that this cascade may affect how an individual, whether animal or human, responds to additional challenges to the immune or metabolic systems, such as infection or high fat food, both ubiquitous realities of modern life. They are also working on models to understand the impact of different kinds of light-dark shifting such as those experienced by flight crews, shift workers, military personnel and medical residents. “We want to know how different patterns affect the brain and body, and if they share similar mechanisms of action,” says Karatsoreos.
More information: Proceedings of the National Academy of Sciences 108: 1657–1662 (January 25, 2011). Disruption of circadian clocks has ramifications for metabolism, brain, and behavior. Ilia N. et al.
Provided by Rockefeller University (news : web)

New findings help explain our most mysterious sense

February 21, 2011 By Kirsten Weir

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Credit: ArnoldReinhold
From your first sip of morning coffee to the minty zing of toothpaste before bed, your tongue is bombarded daily with a flood of flavors. How we disentangle and identify all those tastes is still pretty mysterious. That's starting to change, though, as researchers unlock the secrets of flavor.
Several taste experts spoke at a symposium on "The Science of Eating: Perception and Preference in Human Taste" on February 19 at the annual meeting of the American Association for the Advancement of Science (AAAS), held this year in Washington, D.C.
A couple of decades ago, the established number of basic tastes went from four to five, with the addition of umami -- the savory taste of Parmesan cheese and sundried tomatoes -- to the traditional grouping of salty, sweet, sour, and bitter. But there's much more to flavor than those five tastes.
Most of what we think of as flavor is really aroma. To the taste buds on your tongue, a lemon and a lime are both just sour. It's your nose that tells you which citrus you're swallowing.
Food scientists envision flavor as a medley of factors, including taste, odor, texture, and even irritation -- a familiar component of spicy chilies. "Tastes, aromas, and mouthfeel factors are rich sources of stimulation throughout our lives," said Jane Leland, a food scientist at Kraft Foods in Glenview, Ill., in an interview before the symposium.
Leland took part in the AAAS session along with William Yosses, the White House pastry chef, and Gary Beauchamp, director of the Monell Chemical Senses Center in Philadelphia.
"There are large individual differences in the way we perceive the world," said Beauchamp, also in an interview. "Those differences are due to two interacting sources – genetic variation and individual experience."
Genetically speaking, for instance, certain individuals are inherently more sensitive to bitter flavor compounds. They often abhor broccoli and other bitter vegetables.
Many other factors play a role in shaping our fondness for flavors. Both before and after birth, babies get a hint of the foods their mothers consume via taste and odor compounds that get into amniotic fluid and breast milk. Studies show that children have a preference for flavors they were first exposed to this way, Beauchamp said.
Cultural factors, too, influence which foods you love or hate. If you grew up eating spicy curries or seaweed salad, those preferences can stick with you longer than other cultural carryovers.
"Studies show that in people who emigrate, the last things they give up are those flavor principles," said Richard Mattes, a professor of food and nutrition at Purdue University in West Lafayette, Ind., who did not participate in the AAAS symposium.
We may feel strongly about certain foods, but precisely how we taste them is still an open question. Our taste buds contain a variety of specialized chemical structures, known as receptors, that latch onto molecules characteristic of particular tastes, signaling their presence to our brains. But scientists have not yet identified all the receptors that do this job.
Some researchers have even begun to suspect that there are more than just five basic tastes. According to Mattes, we may also have receptors for compounds such as fat, calcium, and carbon dioxide.
"It's far from proven that these things do in fact have unique taste properties," he said, "but there's a growing body of science that's consistent with that notion."
A recent surprise for taste scientists has been the discovery of receptors for the basic tastes not only on the tongue, but also in the airways and the intestines.
"Scientists believe the receptors throughout the digestive tract may help coordinate the body's hormone response to food nutrients," Leland said.
One such response might be how full we feel after eating certain foods. If that's so, it might be possible one day to combat overeating by finding ways to trick the gut receptors into thinking we've had enough.
It's no surprise that Kraft, like many other food manufacturers, is exploring ways to promote healthy foods while giving consumers the tastes they crave.
"Almost all consumers tell us they want to eat healthier. Yet no one wants to give up their favorite foods or eat foods they don't like," Leland said.
As flavor scientists learn more about taste receptors, they will find better ways to replace ingredients such as salt, sugar and fat, Beauchamp predicted. Chemicals that boost the perception of saltiness, for example, could result in potato chips that taste satisfyingly salty but are actually low in sodium.
Insights from flavor scientists won't necessarily all be applied to making foods healthier, however.
These days, food is often entertainment. "We use food as a form of sensory stimulation and pleasure, and as a basis of social interaction," Mattes said. Gourmet chefs increasingly serve palate-challenging dishes such as ice cream that looks like vanilla but tastes like bacon and eggs.
"It does seem as though the trend has been for novelty, perhaps over palatability," Mattes said. Challenging your tongue can be fun, he added. "But whether you'd want to eat that on any regular basis is another question."
Provided by Inside Science News Service (news : web)

JESUS FUCKING CHRIST ON A BUTT PLUG CROSS

Can mods consider a thread just for ScnTO's posts, without all this anon trolling? I mean Iran can fucking post oodles of shit, why censor ScnTO's pearls of Elron?

When fingers start tapping, the music must be striking a chord

February 19, 2011

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According to University of Toronto speech-language pathologist Luc De Nil, the beat could be revealing such things as how children master one of the most complex tasks of all – speech.
"The rapid and precise muscle movements of speech must be the most intricate, yet poorly understood, of all the sensory-motor skills," says De Nil.
De Nil's interest in finger-tapping came out of his group's previous work on adults who stutter. His team discovered that they have problems in acquiring new and unusual tapping sequences and not just speech. The research suggests an underlying neural basis for the motor deficit.
The researchers tested the abilities of stuttering adults to learn both speech and tapping sequences. In some experiments, the participants were given extensive practice lasting more than one day. Other studies investigated the effects on the accuracy of a speaker's performance when motor learning was disrupted. To follow up, the investigators use magnetic resonance imaging and fMRI to observe and analyze the neural processes underlying speech production in children and adults who stutter.
"We turned to children next because we wanted to know if the adult data was relevant to them and if giving them finger and speech tasks would let us observe motor skills as they develop in both stutterers and non-stutterers."
De Nil will discuss some of the findings at this week's meeting of the American Association for the Advancement of Science in Washington, D.C. He will take part in the session From Freud to fMRI: Untangling the Mystery of Stuttering on Sunday, February 20.
Provided by Natural Sciences and Engineering Research Council

this thread is now about how awesome the human brain is.

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   The matter of the brain is 70% fat
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   Nothing in Dianetics and Scientology is true for you Unless you have observed it And it is true...
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   The Brain doesn't do any thinking...it's a communication switchboard... Do you believe that...
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   Please stop posting all the stupid pictures
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   You are not your brain...can meat think?...are you that meat between your ears?
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   He's busy trying to socially engineer me - BRB telling him my name, address and phone number...
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    Mark Headley doen't look like he's been Fair Gamed but he does look like he had his fair share...
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New model for probing antidepressant actions

February 18, 2011

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medicines such as Prozac, Lexapro and Paxil – work by blocking the serotonin transporter, a brain protein that normally clears away the mood-regulating chemical serotonin. Or so the current thinking goes.
That theory about how selective serotonin reuptake inhibitors (SSRIs) work can now be put to the test with a new mouse model developed by neuroscientists at Vanderbilt University.
These mice, described in the online edition of the Proceedings of the National Academy of Sciences (PNAS), express a serotonin transporter that has been genetically altered so that it does not respond to many SSRIs or cocaine.
In addition to testing the theory about how SSRIs work, the new mouse model could lead to the development of entirely new classes of antidepressant medications, said Randy Blakely, Ph.D., Allan D. Bass Professor of Pharmacology and Psychiatry at Vanderbilt and senior author of the PNAS paper.
"Many antidepressants have been shown to target other proteins besides the serotonin transporter and … their efficacy in treating depression takes many weeks to develop," Blakely said. "There is likely a lot that we don't know about how these drugs act."
To generate the mouse model, Blakely and colleagues at Vanderbilt and the University of Texas Health Science Center at San Antonio first determined exactly which parts of the serotonin transporter protein interact with SSRIs. They took advantage of the fact that the fruit fly expresses a serotonin transporter that is relatively insensitive to the drugs.
By changing the protein's amino acid building blocks, they converted parts of the human serotonin transporter into its fruit fly equivalent, and in so doing identified the single amino acid required for potent binding to many SSRIs as well as to cocaine.
As predicted, the genetically-modified mice displayed normal serotonin transporter levels, and their transporter exhibited normal activity in clearing serotonin from the synapses between nerve cells. But the mice did not respond to Prozac or Lexapro, indicating that the transporter is indeed the specific target of these medications for blocking serotonin inactivation.
"Interestingly, one SSRI, paroxetine (Paxil), retains its normal powerful action on the transporter, revealing that -- at a molecular level -- different antidepressants interact with the transporter in different ways," Blakely said.
The researchers are now evaluating chronic administration of SSRIs to determine how much the transporter contributes to the more clinically relevant, delayed effects of these drugs, as well as for the side effects experience with antidepressant medications.
Because the serotonin transporter in the mouse also lost cocaine sensitivity, the model also may help researchers determine exactly how cocaine acts in the brain. "Perhaps what started as a hunt for better ways to treat depression may also spill over into a better understanding of addiction," Blakely said.
Provided by Vanderbilt University Medical Center (news : web)

Brain function linked to birth size in groundbreaking new study

February 18, 2011

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Scientists have discovered the first evidence linking brain function variations between the left and right sides of the brain to size at birth and the weight of the placenta. The finding could shed new light on the causes of mental health problems in later life.
The research, conducted at the University of Southampton and the Medical Research Council (MRC) Lifecourse Epidemiology Unit at Southampton General Hospital, reveals that children who were born small, with relatively large placentas, showed more activity on the right side of their brains than the left. It is this pattern of brain activity that has been linked with mood disorders such as depression.
The study adds to a growing body of evidence showing that adverse environments experienced by fetuses during pregnancy (indicated by smaller birth size and larger placental size) can cause long-term changes in the function of the brain.
"The way we grow before birth is influenced by many things including what our mothers eat during pregnancy and how much stress they are experiencing. This can have long-lasting implications for our mental and physical health in later life," explains Dr Alexander Jones, an epidemiologist, who led the study at the University of Southampton.
"This is the first time we've been able to link growth before birth to brain activity many years later. We hope this research can begin to shed new light on why certain people are more prone to diseases such as depression."
The neurological responses of 140 children from Southampton, aged between eight and nine, were monitored for the study. Tests evaluated blood flow to the brain in response to increased brain activity, exposing differences in the activity of the two sides. Dr Jones measured tiny fluctuations in the temperature of the tympanic membrane in each ear, which indicate blood flow into different parts of the brain.
Disproportionate growth of the placenta and the fetus is thought to occur in pregnancies where the mother has been experiencing stress or where there have been problems with the availability of nutrients. Previous research has linked this pattern of growth to other diseases such as hypertension and greater physical responses to stress in later life.
The research by Dr Jones and colleagues, has been published in the online science journal, PLoS ONE.
More information: A pdf of the full paper is freely available at: http://www.plosone … entation=PDF
Provided by University of Southampton (news : web)

Mind-moved bionic arm goes on display in US

February 17, 2011

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Todd Kuiken (L), Director of the Center for Bionic Medicine and Director of Amputee Services at The Rehabilitation Institute of Chicago, explains the bionic arm on Glen Lehman (R), a retired sergeant first class in the United States Army.
A bionic prosthetic arm that is controlled by its operator's thoughts and feels like the amputee's lost limb went on display Thursday at a major US science conference.
More than 50 amputees worldwide, many of them military veterans whose limbs were lost in combat, have received such devices since they were first developed by US doctor Todd Kuiken in 2002.
The arm uses technology called Targeted Muscle Reinervation (TMR), which works by rerouting brain signals from nerves that were severed in the injury to muscles that are working and intact.
"What we do is use the nerves that are still left," Kuiken said. "Muscle becomes the biological amplifier."
Glen Lehman, a retired US military sergeant who lost his arm in Iraq, demonstrated the latest technology at the annual conference of the American Association for the Advancement of Science in Washington.
"It feels great, if feels intuitive. It is a lot better than the other prosthetic I have now," said Lehman, whose forearm and elbow were blown off in a Baghdad grenade attack in 2008.
"The other one is still controlled by muscle impulse, you just flex muscle to make it move, it is not intuitive. This arm is more trained to me, whereas the other arm I had to train to it," he said.
"It does feel like my own hand."
Lehman demonstrated for reporters how he could pinch his finger and thumb together, lift his forearm and bend his elbow, and turn his wrist just by thinking about those actions.
Kuiken said more advances, such as the ability to transfer some sensation to the limb, are being studied in the lab but have not yet made it to patients.
Other drawbacks include the inability to sense how hard the battery-powered prosthetic hand is squeezing, but Kuiken said scientists are working on ways to improve the technology with added sensors.
"Our goal would be to put sensors in the prosthesis to, for example, know how hard you are squeezing and then bring that up and have a device squeeze on this area (of the bicep) so the patient has an idea of how hard he is squeezing."

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Glen Lehman (L), a retired sergeant first class in the United States Army who received Targeted Muscle Reinnervation (TMR) surgery after he lost his arm in Iraq, stands with his bionic arm next to LTC Martin Baechler, M.D., a surgeon at Walter Reed Army Medical Center, during a presentation of the latest in TMR, a bionic limb technology.
Kuiken said the team has encountered some technological "challenges" that have slowed progress but is "excited about moving forward."
A series of other efforts to test and improve on these mind-reading robotics, known as brain-computer interfaces, were also showcased at the conference.
Among them, how researchers can now place computer chips on the surface of the brain to interpret neural activity, potentially allowing spinal cord injury patients to control a range of devices from computer games to prosthetics.
Someday, patients who are bed-ridden will be able to wear a special electronic cap that allows them to maneuver a rolling robot carrying a video camera, so that the patient could join in the dinner conversation without leaving the bedroom.
But the stunning technology is anything but easy work for the patients.
According to Jose del R. Millan and his team at the Ecole Polytechnique Federale de Lausanne in Switzerland, in a "typical brain-computer interface (BCI) set-up," users send mental messages of either left, right, or no-command.
"But it turns out that no-command is very taxing to maintain and requires extreme concentration. After about an hour, most users are spent. Not much help if you need to maneuver that wheelchair through an airport," his team said in a statement.
So now researchers are figuring out how to hook up a machine to interpret a user's brain signals and read their intent.
Users are asked to read or speak aloud while thinking of as many left, right or no commands as possible. The technology learns to sift through the fray and figure out when a command has been delivered.
The result "makes multitasking a reality while at the same time allows users to catch a break."
(c) 2011 AFP

Unraveling how prion proteins move along axons in the brain

February 17, 2011

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Researchers at the University of California, San Diego School of Medicine have identified the motors that move non-infectious prion proteins (PrPC) – found within many mammalian cells – up and down long, neuronal transport pathways. Identifying normal movement mechanisms of PrPC may help researchers understand the spread of infectious prions within and between neurons to reach the brain, and aid in development of therapies to halt the transport.
Their study is published in the February 18 edition of the journal Cell.
The small prion protein is found in the cell membrane of brain neurons. The misfolded or infectious form of this protein (also called "scrapie"), is responsible for "mad cow" disease and has also been implicated in Creutzfeldt-Jakob disease in humans. Non-infectious and scrapie forms interact to produce disease; so, in order to help uncover how the infection is spread within and among neuron cells to the brain, the UCSD scientists studied the movement mechanism of normal PrPC in mouse neuronal cells.
"Our work unraveling the normal mechanism of movement of this prion protein will help us understand how the devastating pathogenic versions found in mad cow disease and other prion diseases are formed and transmitted in the brain. Intriguingly, our work may also shed light on what goes wrong in other neurodegenerative diseases such as Alzheimer's disease," said principal investigator Larry Goldstein, PhD, professor of Cellular and Molecular Medicine, Howard Hughes Medical Institute investigator and director of the UC San Diego Stem Cell Program.
It is known that normal prion proteins and infectious prions need to interact in order for prion pathogenesis to occur, though not how or why these interactions occur. Discovering the transport mechanisms of prions is one key to the puzzle of how the two types of proteins interact, and an important question in transport regulation has been how motor activity is controlled in cells.
The prion protein cargo travels on long microtubule tracks along the peripheral and central nervous system nerves toward the terminus, or synapse, in membrane-bound sacs called vesicles. Intracellular transport is often bi-directional, because cargoes regularly reverse their course en route to their final destinations.
The researchers identified the motors driving these vesicles as anterograde Kinesin-1 – which moves only toward the synapse – and dynein, which is retrograde, moving away from the synapse. These two motor proteins assemble on the PrPC vesicles to "walk" them back and forth along the microtubules.
Secondly, they discovered that the back and forth cargo movement is modulated by regulatory factors, rather than by any structural changes to the motor-cargo associations. The study data show that the activity of Kinesin-1 and dynein are tightly coupled, with PrPC vesicles moving at different velocities and for varied lengths along axons. However, the type and amounts of these motor assemblies remain stably associated with stationary as well as moving vesicles, and normal retrograde transport by Kinesin-1 is independent of dynein-vesicle attachment.
The UCSD study of the mechanisms behind normal vesicle movement along the axons in mouse cells might also shed light on other neurodegenerative disease. While Alzheimer's is not generally considered an infectious disease like mad cow disease, emerging data suggest that Tau, amyloid-beta, and alpha-synuclein – proteins implicated in Alzheimer's and Parkinson's disease – have self-propagating fibril structures with prion-like characteristics.
"Whether these toxic molecules spread along neuronal transport pathways in ways similar to the normal prion protein is unknown," said first author Sandra E. Encalada, PhD, of the UCSD Department of Cellular and Molecular Medicine. "But characterization of these normal mechanisms might lead to a way to control movement of intracellular aggregates, and perhaps to therapies for many neurodegenerative diseases."
Provided by University of California - San Diego (news : web)

Researchers find brain insulin plays critical role in the development of diabetes

February 16, 2011

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Researchers from Mount Sinai School of Medicine have discovered a novel function of brain insulin, indicating that impaired brain insulin action may be the cause of the unrestrained lipolysis that initiates and worsens type 2 diabetes in humans. The research is published this month in the journal Cell Metabolism.
Led by Christoph Buettner, MD, Assistant Professor of Medicine in the Division of Endocrinology, Diabetes and Bone Disease at Mount Sinai School of Medicine, the research team first infused a tiny amount of insulin into the brains of rats and then assessed glucose and lipid metabolism in the whole body. In doing so, they found that brain insulin suppressed lipolysis, a process during which triglycerides in fat are broken down and fatty acids are released.
Furthermore, in mice that lacked the brain insulin receptor, lipolysis was unrestrained. While fatty acids are important energy sources during fasting, they can worsen diabetes, especially when they are released after the person has eaten, as happens in people with diabetes. Researchers previously believed that insulin's ability to suppress lipolysis was entirely mediated through insulin receptors expressed on adipocytes, or fat tissue cells.
"We knew that insulin has this fundamentally important ability of suppressing lipolysis, but the finding that this is mediated in a large part by the brain is surprising," said Dr. Buettner. "The major lipolysis-inducing pathway in our bodies is the sympathetic nervous system and here the studies showed that brain insulin reduces sympathetic nervous system activity in fat tissue. In patients who are obese or have diabetes, insulin fails to inhibit lipolysis and fatty acid levels are increased. The low-grade inflammation throughout the body's tissue that is commonly present in these conditions is believed to be mainly a consequence of these increased fatty acid levels."
Dr. Buettner added, "When brain insulin function is impaired, the release of fatty acids is increased. This induces inflammation, which can further worsen insulin resistance, the core defect in type 2 diabetes. Therefore, impaired brain insulin signaling can start a vicious cycle since inflammation can impair brain insulin signaling." This cycle is perpetuated and can lead to type 2 diabetes. Our research raises the possibility that enhancing brain insulin signaling could have therapeutic benefits with less danger of the major complication of insulin therapy, which is hypoglycemia."
Dr. Buettner's team plans to further study conditions that lead to diabetes such as overfeeding to test if excessive caloric intake impairs brain insulin function. A major second goal will be to find ways of improving brain insulin function that could break the vicious cycle by restraining lipolysis and improving insulin resistance. This study is supported by a grant from the National Institutes of Health and the American Diabetes Association. First author of the study is Thomas Scherer, PhD, postdoctoral fellow in the Department of Medicine in the Division of Endocrinology, Diabetes and Bone Disease.
Provided by The Mount Sinai Hospital