Studies Confirm That Serotonin Plays A Role In Many Autism Cases

Mouse models are yielding important clues about the nature of autism spectrum disorders, which impact an estimated one in 110 children in the U.S. In labs at the UT Health Science Center San Antonio, researchers are studying strains of mice that inherently mimic the repetitive and socially impaired behaviors present in these disorders. Georgianna Gould, Ph.D., research assistant professor of physiology in the Graduate School of Biomedical Sciences, is eyeing the role that serotonin plays in autism spectrum disorders.
Serotonin is known for giving a sense of well-being and happiness. It is a neurotransmitter, a chemical that acts like a radio tower in the brain conveying signals among cells called neurons. Thirty percent of autism cases may have a serotonin component. In a recent paper in the Journal of Neurochemistry, Dr. Gould and colleagues showed that a medication called buspirone improved the social behaviors of mice. Buspirone is approved by the U.S. Food and Drug Administration for use in adults as an anti-anxiety and antidepressant adjuvant medication.

Some genetic variations result in diminished transmission of serotonin between neurons. Buspirone increased transmission by partially mimicking the effects of serotonin at cellular sites called receptors.

Reactions to newly encountered mouse
Social interaction behaviors of the mice were measured by placing them in a three-chamber social interaction test and positioning a "stranger" mouse in one of the chambers. Buspirone-treated mice spent more time in the chamber with the stranger mouse than untreated mice and more time sniffing the stranger. "No animal model is completely characteristic of humans, and we're far from saying that buspirone is a treatment for behaviors of autistic people," Dr. Gould said. "But this does offer further proof that serotonin is involved in a significant proportion of autism cases."

Support from the San Antonio Area Foundation made the project possible. Co-authors of the journal article are Julie Hensler, Ph.D., and Teri Frosto Burke, M.S., of the pharmacology department at the Health Science Center; Lynette Daws, Ph.D., of the university's physiology department in whose lab the work was conducted; and Robert Benno, Ph.D., and Emmanuel Onaivi, Ph.D., of the biology department at William Paterson University in Wayne, N.J.

2nd serotonin-related avenue

Dr. Gould now plans to study the impact of a diet rich in the amino acid, tryptophan, on the social behavior of the mice. Tryptophan is a biochemical precursor of serotonin, which means it is converted into serotonin during the metabolic process. Foods such as turkey are rich in tryptophan.

"We are going to supplement the diet of mice with tryptophan to see if behavior improves, and also reduce it to see if behavior worsens," Dr. Gould said. The future study of tryptophan is funded by the Morrison Trust, a San Antonio trust that lists nutrition as one of its topics of interest.

Source: University of Texas Health Science Center at San Antonio

Brain areas for depression

Overlooked Brain Area Is An Important Locus Of Depression


A team of neuroscientists at Cold Spring Harbor Laboratory (CSHL), Brookhaven National Laboratory (BNL) and UC San Diego (UCSD) has collected evidence suggesting that a previously overlooked portion of the brain could be a prime locus of human depression. In two rat models of human depression, the scientists have demonstrated that neurons in a tiny area in the central brain called the lateral habenula (LHb) are hyperactive.
Specifically, as the team reports today online ahead of print in the journal Nature, excitatory synaptic inputs onto neurons in the LHb are enhanced in "depressed" animals, a finding they regard significant because this excitation in turn causes the inhibition of "downstream targets" - including neurons in a part of the brain called the ventral tegmental area (VTA), important in the brain's reward system and heavily populated by dopamine neurons.

Furthermore, the team, which includes Professor Fritz Henn of CSHL and BNL and Assistant Professor Bo Li of CSHL, as well as Professor Roberto Malinow of UCSD, was able to use an analog of deep brain stimulation (DBS), a novel form of electrical stimulation involving the implantation of electrodes into a specific brain area, to reverse depression-like symptoms in the rats.

DBS is an important new experimental modality of treatment for refractory depression in people, as well as a potentially important approach to treat other neurophysiological disorders, most notably Parkinson's disease. The team's results point to the LHb as a potential therapeutic target for DBS. A series of ongoing experiments in depression at other laboratories, which have shown promise in a small number of human patients, have used DBS to target an area of the cingulate cortex called Brodman's Area 25. Henn and colleagues in Germany last year reported success in treating one case of intractable human depression with DBS, targeting the LHb.

The animal models used in the team's rat experiments displayed a behavior called learned helplessness. The rats were stressed in ways that were unpredictable and inescapable; over time, they developed depression-like symptoms, notably a lack of motivation to evade unpleasant stress. "It's not a perfect model of human depression by any means," says Li, "but it is very valuable, for it does enable us to study the neural mechanisms of certain aspects of depression in people."

The team's most important decision was to study the lateral habenula. "This is an area of the brain that has often been overlooked, perhaps because of its size." Li noted, "It covers an area only about 1-2 mm across." So far only two brain imaging studies have implicated the LHb in depression because of the difficulty in resolving it using existing technologies such as PET and fMRI..

Close Friends Light Up Your Medial Prefrontal Cortex Brain Region

title of this article may not catch on as a song lyric, but new neurobiology research shows close friends can cause more of a response in brain regions such as the medial prefrontal cortex than strangers can.

The research subjects’ brain regions responded more to questions regarding their close friends than they did to strangers with similar interests. The experiments attempt to show that social closeness is used more than similarity of beliefs when evaluating others in some tasks relying on the medial prefrontal cortex region of the brain.The research is explained more thoroughly below.

Imaging study shows brain responds more to close friends

People’s brains are more responsive to friends than to strangers, even if the stranger has more in common, according to a study in the Oct. 13 issue of the Journal of Neuroscience. Researchers examined a brain region known to be involved in processing social information, and the results suggest that social alliances outweigh shared interests.

In a study led by graduate student Fenna Krienen and senior author Randy Buckner, PhD, of Harvard University, researchers investigated how the medial prefrontal cortex and associated brain regions signal someone’s value in a social situation. Previous work has shown that perceptions of others’ beliefs guide social interactions. Krienen and her colleagues wondered whether these brain regions respond more to those we know, or to those with whom we share similar interests.
“There are psychological and evolutionary arguments for the idea that the social factors of ‘similarity’ and ‘closeness’ could get privileged treatment in the brain; for example, to identify insiders versus outsiders or kin versus non-kin,” Krienen said. “However, these results suggest that social closeness is the primary factor, rather than social similarity, as previously assumed.”

The researchers first imaged the brain activity of 32 participants as they judged how well lists of adjectives described their personalities. This helped to identify brain regions that respond to personally relevant information. In separate experiments, 66 different participants provided personality information about themselves and two friends — one friend whom they believed had similar preferences and one believed to be dissimilar.
The authors made up biographies of similar and dissimilar strangers for each volunteer based on their personality profiles. Then, while in a scanner, they played a game similar to the TV show “The Newlywed Game,” in which participants predicted how another person would answer a question. For example, would a friend or stranger prefer an aisle or window seat on a flight?The authors found activity in the medial prefrontal cortex increased when people answered questions about friends. Notably, whether the person had common interests made no difference in brain response.
“In all experiments, closeness but not similarity appeared to drive responses in medial prefrontal regions and associated regions throughout the brain,” Krienen said. “The results suggest social closeness is more important than shared beliefs when evaluating others.”Read Montague, PhD, of Baylor College of Medicine, an expert on decision-making and computational neuroscience, said the study’s large number of participants and experimental approach makes it a solid contribution to the field. “The authors address an important component of social cognition; the relevance of people close to us,” Montague said.

The research was supported by the National Institute on Aging, the Howard Hughes Medical Institute, the Simons Foundation, the U.S. Department of Defense, and an Ashford Graduate Fellowship in the Sciences.

Contact: Kat Snodgrass Society for Neuroscience , Fenna Krienen and Randy Buckner Harvard University

Source: Society for Neuroscience

Is Angiogenesis the key to Cancer

First Clinical Trial of Human Embryonic Stem Cell Therapy in the World BeginsHuman

Embryonic stem cell therapy is being tried on a human for the first time in a new clinical trial. This is the first clinical trial of its kind in the world.The first patient is reported as a patient in an Atlanta spinal cord and brain injury rehabilitation hospital. The patient’s injuries were between 7-14 days old when the first injections were given. To take part in the study, the patient had to have suffered a spinal or brain injury that resulted in paralysis from the chest down.

This patient has been injected with cells derived from human embryonic stem cells obtained from a fertility clinic. Researchers are optimistic this human embryonic stem cell therapy will not only help alleviate the symptoms of the injury, but permanently repair the damage that caused the paralysis from the spinal cord injury.This is a huge step for regenerative medicine, embryonic stem cell research, spinal cord and brain injury therapy and science in general.

Geron Initiates Clinical Trial of Human Embryonic Stem Cell-Based TherapyFirst Patient Treated at Shepherd Center in Atlanta.Geron Corporation today announced the enrollment of the first patient in the company’s clinical trial of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells, GRNOPC1. The primary objective of this Phase I study is to assess the safety and tolerability of GRNOPC1 in patients with complete American Spinal Injury Association (ASIA) Impairment Scale grade A thoracic spinal cord injuries. Participants in the study must be newly injured and receive GRNOPC1 within 14 days of the injury.
The patient was enrolled at Shepherd Center, a 132-bed spinal cord and brain injury rehabilitation hospital and clinical research center in Atlanta, GA. Shepherd Center is one of seven potential sites in the United States that may enroll patients in the clinical trial.
“Initiating the GRNOPC1 clinical trial is a milestone for the field of human embryonic stem cell-based therapies,” said Thomas B. Okarma, Ph.D., M.D., Geron’s president and CEO. “When we started working with hESCs in 1999, many predicted that it would be a number of decades before a cell therapy would be approved for human clinical trials. This accomplishment results from extensive research and development and a succession of inventive steps to enable production of cGMP master cell banks, scalable manufacture of differentiated cell product, and preclinical studies in vitro and in animal models of spinal cord injury, leading to concurrence by the FDA to initiate the clinical trial.”

“We are pleased to have our patients participating in this exciting research,” said Donald Peck Leslie, M.D., medical director, Shepherd Center. “Our medical staff will evaluate the patients’ progress as part of this study. We look forward to participating in clinical trials that may help people with spinal cord injury.”David Apple, M.D., Shepherd Center’s medical director emeritus and principal investigator of the trial at Shepherd Center, said, “This clinical trial represents another step forward in Shepherd Center’s involvement in an attempt to find a cure for paralysis in people with spinal cord injury. Shepherd Center is an ideal place to conduct this study because of our clinical expertise and the volume of patients referred here for rehabilitation care.”

In addition to Shepherd Center, Northwestern Medicine in Chicago, IL is also open for patient enrollment. As additional trial sites come online and are ready to enroll patients, they will be listed on the Patient Information pages of Geron’s website and on the NIH clinical trials registry, ClinicalTrials.gov.
Further information on the criteria for patient eligibility for the study is also available on ClinicalTrials.gov.

About Spinal Cord Injury



Spinal Cord Injury (SCI) is caused by trauma to the spinal cord that results in a loss of such functions as locomotion, sensation or bowel/bladder control. A traumatic blow to the spine can fracture or dislocate vertebrae that may cause bone fragments or disc material to injure the nerve fibers and damage the glial cells that insulate the nerve fibers in the spinal cord. Most human SCIs are contusions (bruises) to the cord, rather than a severance of the nerve fibers. Every year approximately 12,000 people in the U.S. sustain spinal cord injuries. The most common causes are automobile accidents, falls, gunshot wounds and sports injuries.

About GRNOPC1
GRNOPC1 contains hESC-derived oligodendrocyte progenitor cells that have demonstrated remyelinating and nerve growth stimulating properties leading to restoration of function in animal models of acute spinal cord injury. Preclinical studies showed that administration of GRNOPC1 significantly improved locomotor activity and kinematic scores of animals with spinal cord injuries when injected seven days after the injury. Histological examination of the injured spinal cords treated with GRNOPC1 showed improved axon survival and extensive remyelination surrounding the rat axons. For more information about GRNOPC1, visit www.geron.com/GRNOPC1Trial/.

Sources:CNN, Geron

Brain can learn to overcome sleep apnea: U of T scientist

From sound science to sound sleep

By Mike Kennedy

New research from U of T could provide some restful nights for the 18 million North Americans who suffer from obstructive sleep apnea. In a recent study that appeared in the Journal of Neuroscience, U of T scientists demonstrated that repeated obstruction of the airways requires release of the brain chemical noradrenaline. The release of this chemical helps the brain learn to breathe more effectively and purposefully.

“What we showed is that repeated disruption of normal lung activity - what happens during sleep apnea - triggers a form of learning that helps you breathe better. This type of brain plasticity could be harnessed to help overcome the breathing insufficiency that typifies sleep apnea” said Professor John Peever of cell and systems biology and lead author of the study.

In order to mimic the experience of severe sleep apnea, the scientists induced short 15-second apneas in sedated rats by repeatedly restricting airflow into the lungs. They found repeated apneas caused the brain to progressively trigger more forceful contraction of the respiratory muscles, which caused an increase in breathing. This increase in breathing lasted for over an hour.
Peever said it seems the brain is using the unwanted side-effects of sleep apnea to help it learn to prevent future apneas by increasing the depth of breathing. This study also pinpointed the brain chemical that allows this type of plasticity to occur. They found that noradrenaline is required in the case of repeated apneas to cause brain plasticity and enhance breathing.
These findings are important because they suggest that artificial manipulation with common drugs that affect noradrenaline levels in the brain could also help improve breathing in patients suffering from sleep apnea. This work could serve as the potential basis for developing the long sought after pill for sleep apnea.

Moderate Exercise Enhances Connectivity in Brain Circuits

A new study published in Frontiers in Aging Neuroscience has proven that moderate exercise can help to enhance connectivity in brain circuits. Additionally, exercise can help to improve cognition and combat decline in brain functions associated with aging. Attention, couch potatoes! Walking boosts brain connectivity, function

A group of “professional couch potatoes,” as one researcher described them, has proven that even moderate exercise in this case walking at one’s own pace for 40 minutes three times a week can enhance the connectivity of important brain circuits, combat declines in brain function associated with aging and increase performance on cognitive tasks.

The study, in Frontiers in Aging Neuroscience, followed 65 adults, aged 59 to 80, who joined a walking group or stretching and toning group for a year. All of the participants were sedentary before the study, reporting less than two episodes of physical activity lasting 30 minutes or more in the previous six months. The researchers also measured brain activity in 32 younger (18- to 35-year-old) adults.

Rather than focusing on specific brain structures, the study looked at activity in brain regions that function together as networks.“Almost nothing in the brain gets done by one area it’s more of a circuit,” said University of Illinois psychology professor and Beckman Institute Director Art Kramer, who led the study with kinesiology and community health professor Edward McAuley and doctoral student Michelle Voss. “These networks can become more or less connected. In general, as we get older, they become less connected, so we were interested in the effects of fitness on connectivity of brain networks that show the most dysfunction with age.”

Neuroscientists have identified several distinct brain circuits. Perhaps the most intriguing is the default mode network (DMN), which dominates brain activity when a person is least engaged with the outside world either passively observing something or simply daydreaming.Previous studies found that a loss of coordination in the DMN is a common symptom of aging and in extreme cases can be a marker of disease, Voss said.

“For example, people with Alzheimer’s disease tend to have less activity in the default mode network and they tend to have less connectivity,” she said. Low connectivity means that the different parts of the circuit are not operating in sync. Like poorly trained athletes on a rowing team, the brain regions that make up the circuit lack coordination and so do not function at optimal efficiency or speed, Voss said.

In a healthy young brain, activity in the DMN quickly diminishes when a person engages in an activity that requires focus on the external environment. Older people, people with Alzheimer’s disease and those who are schizophrenic have more difficulty “down-regulating” the DMN so that other brain networks can come to the fore, Kramer said.
A recent study by Kramer, Voss and their colleagues found that older adults who are more fit tend to have better connectivity in specific regions of the DMN than their sedentary peers. Those with more connectivity in the DMN also tend to be better at planning, prioritizing, strategizing and multi-tasking.

The new study used functional magnetic resonance imaging (fMRI) to determine whether aerobic activity increased connectivity in the DMN or other brain networks. The researchers measured participants’ brain connectivity and performance on cognitive tasks at the beginning of the study, at six months and after a year of either walking or toning and stretching.

At the end of the year, DMN connectivity was significantly improved in the brains of the older walkers, but not in the stretching and toning group, the researchers report. The walkers also had increased connectivity in parts of another brain circuit (the fronto-executive network, which aids in the performance of complex tasks) and they did significantly better on cognitive tests than their toning and stretching peers.
Previous studies have found that aerobic exercise can enhance the function of specific brain structures, Kramer said. This study shows that even moderate aerobic exercise also improves the coordination of important brain networks.

“The higher the connectivity, the better the performance on some of these cognitive tasks, especially the ones we call executive control tasks things like planning, scheduling, dealing with ambiguity, working memory and multitasking,” Kramer said. These are the very skills that tend to decline with aging, he said.

This study was supported by the National Institute on Aging at the National Institutes of Health.
Editor’s note: To contact Art Kramer, call 217-244-8373; e-mail a-kramer@illinois.edu. To reach Michelle Voss, call 217-244-4461; e-mail mvoss@illinois.edu.

The paper, “Plasticity of Brain Networks in a Randomized Intervention Trial of Exercise Training in Older Adults,” is available online: http://frontiersin.org/Aging_Neuroscience/10.3389/fnagi.2010.00032/abstract

Contact: Diana Yates- Source: University of Illinois at Urbana-Champaign

Tribute to Cloning

MRI and love

Brainsight

Babies’ brains and language

First Hand Experience of a major Stroke

JNS Article Analyzes The Role Of Helmets In Reducing Skull Fractures Incurred By Children In Skiing And Snowboarding Accidents

A compelling clinical article published online in the March 2011 issue of Journal of Neurosurgery: Pediatrics, entitled Helmet Use Reduces Skull Fractures in Skiers and Snowboarders Admitted to the Hospital discusses skull fractures incurred by young skiers and snowboarders and the role helmets play in reducing these head injuries. Authors are Anand I. Rughani, MD, Chih Lin, MD, Michael A. Horgan, MD, Bruce I. Tranmer, MD, Ryan P. Jewell, MD (Division of Neurosurgery, University of Vermont, Burlington, Vt.); William J. Ares, BS (College of Medicine, University of Vermont, Burlington, Vt.); Deborah A. Cushing, MPH, and Jeffrey E. Florman, MD (Neurosciences Institute, Maine Medical Center, Portland, Maine). .

Severe head trauma is the most frequent cause of death and severe disability in skiers and snowboarders and accounts for about 15 percent of all skiing and snowboarding related injuries. Although helmet use is apparently increasing, it remains far from universal. The authors cite a large survey of skiers and snowboarders of all ages in western United States and Canada published in 2003 which indicated that 12.1 percent wore helmets, and more recently a 2008 study that indicated that as many as 42 percent of children in the state of New York wore helmets. At present, there are no current state laws mandating helmets for skiers or snowboarders.

The role of protective helmets in reducing ski and snowboard injuries is a matter of active epidemiological research and some debate. Several large observational surveys collectively suggest that the use of helmets reduces the need to be evacuated by ambulance or visit a hospital. A recent meta-analysis concludes that helmet use reduces head injuries by 35 percent, and another recent meta-analysis suggests head injury reductions ranging from 15-60 percent. However, none of these studies have established whether or not helmet use in skiers and snowboarders reduces the incidence of head injuries seen on CT scans. The present study is the first to analyze head injury patterns sustained by helmeted versus unhelmeted skiers and snowboarders under the age of 21, as confirmed on CT scans.

The authors reviewed data on head injured skiers and snowboarders treated at two level 1 trauma centers in New England from 2003-2009. The authors focused their research on 57 children (age 21 and younger). The primary endpoints of interest were the presence of CT findings that included epidural hematoma, subdural hematoma, other traumatic intracranial hemorrhage, and skull fractures. The secondary endpoints of interest were the presence of cervical spine injury, the need for a neurosurgical procedure, the admission location, length of hospital stay, discharge location, and incidence of death. Noteworthy results culled from this in-depth analysis:

- Helmet usage: 19 helmeted (33.3 percent), 38 unhelmeted (66.7 percent)

- Helmet usage by sport: 30.8 percent skiers, 35.5 percent snowboarders

- Skull Fractures: 5.2 percent of helmeted patients suffered skull fractures versus 36.8 percent of unhelmeted patients.

- Helmeted fracture patterns: 1 non-depressed skull fracture

- Unhelmeted fracture patterns: 14 skull fractures, 8 of which were depressed


The authors cite several studies that attributed a majority of skiing fatalities to head injury:

- Utah study: 88.9 percent of fatal injuries attributed to head injury

- Vermont study: 87.5 percent of fatal injuries attributed to head injury

- Alberta study: 80.0 percent of fatal injuries attributed to head injury

- Switzerland study: 80.0 percent of fatal injuries attributed to head injury

A review of other studies shows compelling evidence that skull fractures sustained by children in skiing and snowboarding pose serious risk. A New Hampshire study reported that 71.1 percent of all children involved in a ski accident and admitted to the hospital had suffered a skull fracture. An analysis of 16 fatal ski injuries in Vermont from 1980-1986 revealed that of the 16 deaths, 14 patients had suffered head injuries and 13 of those were associated with skull fractures.

"We are able to show that helmets are associated with reduced skull fractures in skiers and snowboarders seen at the hospital. Given that skull fractures can be an indication of severe brain injury and sometimes associated with intracranial bleeding, a reduction in skull fractures is a compelling finding. Furthermore, we did not see any increase in the risk of cervical spine injuries as some might predict. Although not a focus of our work, other research has shown that helmet use in skiers and snowboarders does not increase risk-taking behavior. This work supports the protective role of helmets in skiers and snowboarders," said Dr. Rughani.

The authors report no conflict of interest.
Source: American Association of Neurological Surgeons (AANS)

Alzheimers and Human Tau

Alzheimer’s Symptoms Reversed in Mice with Human Tau GenesAlzheimer’s disease research has lead to important findings involving the tau gene and the possibility of reversing the disease’s progression.
The researchers used transgenic mice with two different human tau gene variants. One variant leads to tau proteins that can become entangled, the other leads to tau proteins that cannot.

The mice with tau genes that could not be entangled did not develop Alzheimer’s disease symptoms. Mice with tau genes that lead to entangled proteins did develop Alzheimer’s disease symptoms.
When the group of mice with Alzheimer’s disease symptoms had their tau genes switched off, the symptoms were reversed. The symptoms such as dementia, memory loss and reduction of synapses were drastically reversed when the tau genes were switched off just a few weeks earlier.
More animal studies are in the works to further investigate these findings. The ability to produce and reverse Alzheimer’s disease symptoms using human tau genes in mice is likely to be extremely beneficial to Alzheimer’s disease research as mice tau proteins don’t usually tangle. These results should help produce even better models of human Alzheimer’s disease to study and help focus in on better treatments.

This research is extremely promising to those interested in reversing Alzheimer’s disease in humans as it shows that reversal of many symptoms is possible in mouse models now.
Many more important details are presented in the release below.


Tau-induced memory loss in Alzheimer’s mice is reversible

Amyloid-beta and tau protein deposits in the brain are characteristic features of Alzheimer disease. The effect on the hippocampus, the area of the brain that plays a central role in learning and memory, is particularly severe. However, it appears that the toxic effect of tau protein is largely eliminated when the corresponding tau gene is switched off. Researchers from the Max Planck Research Unit for Structural Molecular Biology at DESY in Hamburg have succeeded in demonstrating that once the gene is deactivated, mice with a human tau gene, which previously presented symptoms of dementia, regain their ability to learn and remember, and that the synapses of the mice also reappear in part. The scientists are now testing active substances to prevent the formation of tau deposits in mice. This may help to reverse memory loss in the early stages of Alzheimer disease – in part, at least. (Journal of Neuroscience, February 16, 2011)

Whereas aggregated amyloid-beta protein forms insoluble clumps between the neurons, the tau protein accumulates inside them. Tau protein stabilises the tube-shaped fibers of the cytoskeleton, known as microtubules, which provide the “rails” for cellular transport. In Alzheimer disease, excess phosphate groups cause the tau protein to malfunction and form clumps (the ‘neurofibrillary tangles’). As a result, nutrient transport breaks down and the neurons and their synapses die off. This process is accompanied by the initial stage of memory loss.
Together with colleagues from Leuven, Hamburg and Erlangen, Eva and Eckhard Mandelkow’s team from the Max Planck Research Unit for Structural Molecular Biology generated regulatable transgenic mice with two different human tau gene variants that can be switched on and off again: one group was given a form of the protein that cannot become entangled (anti-aggregant), and a second was provided with the code for the strongly aggregating protein variant (pro-aggregant). The mice with the first form developed no Alzheimer symptoms; the rodents that were given the pro-aggregant tau developed the disease.

The scientists measured the mice’s memory loss with the help of a swimming test: the healthy mice quickly learn how to find a life-saving platform located under the surface of the water in a water basin. In contrast, the transgenic animals, which have the additional pro-aggregant tau gene paddle aimlessly around the basin until they accidentally stumble on the platform; they require over four times more time to do this than their healthy counterparts. However, if the mutated toxic tau gene is switched off again, the mice learn to reach “dry land” with ease just a few weeks later. As a control, the mice with the anti-aggregant form of tau have no defects in learning, just as normal non-transgenic mice.
Surprising tissue results

Tissue tests showed that, as expected, no tau clumps had formed in the brains of the first group of mice expressing anti-aggregant tau. In the second group – the mice suffering from Alzheimer’s – co-aggregates from human tau and “mouse tau” were formed – against expectations, because tau protein from mice does not usually aggregate. “Even more astonishingly, weeks after the additional gene had been switched off, the aggregated human tau had dissolved again. However, the ‘mouse tau’ remained clumped. Despite this, the mice were able to learn and remember again,” says Eckhard Mandelkow. More precise tests revealed that new synapses had actually formed in their brains.

The scientists concluded from this that mutated or pathological tau can alter healthy tau. It appears that pro-aggregant tau can act similar to a crystal nucleus – once it has started to clump up, it drags neighboring “healthy” tau into the clumps as well. This is what makes the process so toxic to the neurons. “The really important discovery here, however, is that the progression of Alzheimer’s disease can be reversed in principle – at least at an early stage of the illness before too many neurons have been destroyed,” explains Eva Mandelkow who, together with her husband, will be awarded the Potamkin Prize 2011 for Alzheimer’s disease research, which is sponsored by the American Academy of Neurology.

The aggregation of tau proteins, however, cannot simply be switched off in humans the way it can in the transgenic mice. Nevertheless, special substances exist that could dissolve the tau aggregates. By screening 200,000 substances, the Hamburg researchers have already identified several classes of active substances that could re-convert the tau aggregates into soluble tau. These are now being tested on animals.

Details about this article:

Original Article: Tau-induced Defects in Synaptic Plasticity, Learning and Memory are reversible in Transgenic Mice after Switching off the Toxic Tau Mutant

Astrid Sydow, Ann Van der Jeugd, Fang Zheng, Tariq Ahmed, Detlef Balschun, Olga Petrova, Dagmar Drexler, Lepu Zhou, Gabriele Rune, Eckhard Mandelkow, Rudi D’Hooge, Christian Alzheimer, Eva-Maria Mandelkow

Journal of Neuroscience, February 16, 2011
Contacts: Dr. Eva-Maria Mandelkow & Prof. Dr. Eckhard Mandelkow - Max Planck Research Unit for Structural Molecular Biology at DESY

Source: Max Planck

Damage to the brain illustrates brain function

Parkinson's hope:Stem cells delivered in Nasal spray

Stem Cells Delivered in Nasal Spray Ease Parkinson’s Disease Symptoms in RatsScientists have shown that stem cells delivered to rats via a nasal spray lead to an improvement of motor functions in rats with Parkinson’s disease like symptoms.


Mesenchymal stem cells sprayed into the rat noses migrated to the brain and survived for at least 6 months. Dopamine levels increased in previously damaged areas and motor functions improved up to 68% of normal in the stem cell treated rats.

A nasal spray delivery system for stem cells could help avoid problems related to surgical implantation of stem cells. This new method could also make repeated stem cell treatments much safer.

More general information is provided in the release below.

Dramatic Improvement in Parkinson Disease Symptoms Following Intranasal Delivery of Stem Cells to Rat Brains

Successful intranasal delivery of stem cells to the brains of rats with Parkinson disease yielded significant improvement in motor function and reversed the dopamine deficiency characteristic of the disease. These highly promising findings, reported in Rejuvenation Research, a peer-reviewed journal published by Mary Ann Liebert, Inc. highlight the potential for a noninvasive approach to cell therapy delivery in Parkinson disease–a safer and effective alternative to surgical transplantation of stem cells. The article is available free online.

In this groundbreaking study, mesenchymal stem cells (MSCs) delivered via the nose preferentially migrated to the brain and were able to survive for at least 6 months. Substantial improvement in motor function—up to 68% of normal—was reported in the MSC-treated rat model of Parkinson disease. Levels of the neurotransmitter dopamine were significantly higher in affected rat brain regions exposed to MSCs compared to the non-treated brain regions, reported Lusine Danielyan and an international team of researchers from University Hospital of Tübingen, University of Göttingen Medical School, and University of Tübingen (Stuttgart, Germany; HealthPartners Research Foundation, St. Paul, MN; German University in Cairo, Egypt; Harvard University, Cambridge, MA; Institute of Molecular Biology NAS RA, Yerevan, Armenia; and Geneva University Hospital, Switzerland.

The authors present their findings in the article, “Therapeutic Efficacy of Intranasally Delivered Mesenchymal Stem Cells in a Rat Model of Parkinson Disease.” They explain that intranasal delivery of MSCs avoids the tissue trauma and related inflammation and brain swelling associated with surgical implantation of therapeutic stem cells. Importantly, this noninvasive delivery method would also make it possible to provide repeated stem cell treatments over time.

Rejuvenation Research, the Official Journal of the European Society of Preventive, Regenerative and Anti-Aging Medicine (ESAAM) and the World Federation & World Virtual Institute of Preventive & Regenerative Medicine (PYRAMED),is an authoritative, peer-reviewed journal published bimonthly in print and online. Led by Editor-in-Chief Aubrey D.N.J. de Grey, PhD, SENS Foundation, Cambridge,UK, the Journal publishes cutting-edge work on the development of rejuvenation therapies in the laboratory and clinic and explores the molecular and cellular mechanisms behind these novel therapeutic approaches.

ontact: Vicki CohnC - Mary Ann Liebert, Inc., Publishers

Source: Mary Ann Liebert, Inc., Publishers

Heart and Brain for Valentine's Day

JPEG For The Mind: How The Brain Compresses Visual Information

Most of us are familiar with the idea of image compression in computers. File extensions like ".jpg" or ".png" signify that millions of pixel values have been compressed into a more efficient format, reducing file size by a factor of 10 or more with little or no apparent change in image quality. The full set of original pixel values would occupy too much space in computer memory and take too long to transmit across networks.
The brain is faced with a similar problem. The images captured by light-sensitive cells in the retina are on the order of a megapixel. The brain does not have the transmission or memory capacity to deal with a lifetime of megapixel images. Instead, the brain must select out only the most vital information for understanding the visual world.
In the online issue of Current Biology, a Johns Hopkins team led by neuroscientists Ed Connor and Kechen Zhang describes what appears to be the next step in understanding how the brain compresses visual information down to the essentials.
They found that cells in area "V4," a midlevel stage in the primate brain's object vision pathway, are highly selective for image regions containing acute curvature. Experiments by doctoral student Eric Carlson showed that V4 cells are very responsive to sharply curved or angled edges, and much less responsive to flat edges or shallow curves.
To understand how selectivity for acute curvature might help with compression of visual information, co-author Russell Rasquinha (now at University of Toronto) created a computer model of hundreds of V4-like cells, training them on thousands of natural object images. After training, each image evoked responses from a large proportion of the virtual V4 cells - the opposite of a compressed format. And, somewhat surprisingly, these virtual V4 cells responded mostly to flat edges and shallow curvatures, just the opposite of what was observed for real V4 cells.

The results were quite different when the model was trained to limit the number of virtual V4 cells responding to each image. As this limit on responsive cells was tightened, the selectivity of the cells shifted from shallow to acute curvature. The tightest limit produced an eight-fold decrease in the number of cells responding to each image, comparable to the file size reduction achieved by compressing photographs into the .jpeg format. At this level, the computer model produced the same strong bias toward high curvature observed in the real V4 cells.
Why would focusing on acute curvature regions produce such savings? Because, as the group's analyses showed, high-curvature regions are relatively rare in natural objects, compared to flat and shallow curvature. Responding to rare features rather than common features is automatically economical. Despite the fact that they are relatively rare, high-curvature regions are very useful for distinguishing and recognizing objects, said Connor, a professor in the Solomon H. Snyder Department of Neuroscience in the School of Medicine, and director of the Zanvyl Krieger Mind/Brain Institute.

"Psychological experiments have shown that subjects can still recognize line drawings of objects when flat edges are erased. But erasing angles and other regions of high curvature makes recognition difficult," he explained Brain mechanisms such as the V4 coding scheme described by Connor and colleagues help explain why we are all visual geniuses.

"Computers can beat us at math and chess," said Connor, "but they can't match our ability to distinguish, recognize, understand, remember, and manipulate the objects that make up our world." This core human ability depends in part on condensing visual information to a tractable level. For now, at least, the brain format seems to be the best compression algorithm around.

Source: Lisa DeNike -Johns Hopkins University

Diet Pop and Strokes

A study just presented at the American Stroke Assn.’s International Stroke Conference reported a link between the amount of diet soda someone drinks and the risk of having a stroke or heart attack.

Here’s the outline of the study, which was started in 2003, and what it found:

A total of 2,564 people in the study were asked about their intake of sodas (among other questions) at the start of the study. After nine years, 559 cardiovascular events had occurred, and those who had reported drinking diet soda every day had a 60% higher rate of these events, which included various forms of stroke as well as heart attacks.

The scientists adjusted for certain factors, such as age, sex, race, smoking, exercise, alcohol and daily calories. When they added additional factors to do with heart disease risk, such as metabolic syndrome, the risk was still 48% higher for the daily-diet-soda-drinking group. (Metabolic syndrome is a group of factors that can include extra weight around the waist and the inability to efficiently process blood sugar.)

“If our results are confirmed with future studies, then it would suggest that diet soda may not be the optimal substitute for sugar-sweetened beverages for protection against vascular outcomes,” noted the study lead author, Hannah Gardener of the University of Miami School of Medicine, in a release from the stroke association. She made that point also in news reports, such as one written up by WebMD.

It’s worth noting, as some scientists did, that this is a link, not proof of cause and effect. After all, there are many things that people who slurp diet sodas every day are apt to do – like eat a lousy diet — and not all of these can be adjusted for, no matter how hard researchers try. Maybe those other factors are responsible for the stroke and heart attack risk, not the diet drinks. (Those who drink daily soda of any stripe, diet or otherwise, are probably not the most healthful among us.)

Here’s one comment from Dr. Steven Greenberg, a professor of neurology at Harvard Medical School and vice-chairman of the stroke-meeting conference committee: “You try to control for everything but you can’t.” (It’s from the report at WebMD.)

Second, the link depended on self-reported food intake – and self reports are not always that reliable.

Third, the self-report was at the start of the study. Habits do change over time.

This isn’t the first report suggesting a potential link to heart health, however, as fellow Times blogger Karen Kaplan noted in an item in January. The famous Framingham heart study has also reported a link between people who drank sodas -- diet or otherwise – and the risk for metabolic syndrome. I guess we'll learn more as the months and years unfold -- if future studies can tease apart all the lifestyle factors that may be linked to a soda-guzzling habit.

In the meantime, water doesn't prime us to expect cloying sweetness with every mouthful. And sodas --diet or otherwise -- can certainly do that.

Copyright © 2011, Los Angeles Times

Forgetfulness - a poem which captures the pain and frustration of forgetfulness

Poetry:

Oyster-tecture

Myth Busters- Can You dip your hand into molten lead? Yes?

Noam Chomsky and Wikileaks

Noam Chomsky and wikileaks

War on bacteria

 Frisky bacteria war on drugs revealed By James Gallagher

Health reporter, BBC News

Ever since medicine declared war on bacteria with the discovery of penicillin, the two have been locked in an arms race.Antibiotics are met by resistance from germs; so researchers develop new drugs and germs become resistant again.Now some scientists believe genetics will be the new weapon in the fight, with doctors consulting bacterial genomes when treating disease.This week a team at the Wellcome Trust Sanger Institute published a paper in the journal Science, which they say shows the first genetic picture of the evolutionary war between medicine and bacteria.

"Potentially every time someone is ill we could isolate the genome of a bacterial infection” Bacterial genetics can be tricky. With humans, one person's DNA is passed on to their children, then to their children, and so on down the family tree.
Bacteria are altogether more frisky.

They pass DNA onto their descendants when they divide in two, but they also swap DNA with other bacteria, changing their genetic code. It is like popping to the shop and changing eye colour with someone at the checkout.This study has managed to tease out the differences between the two ways of passing on DNA in Streptococcus pneumoniae and draw its family tree.

From the lab to the hospital

The researchers were able to show how the species responded to different antibiotics, how it became resistant, where it became resistant and how the resistance spread around the world.It is the first time the whole of a genome has been studied to measure the genetic response to medicine. Other studies have come to some of the same conclusions, but as a review in the same journal said: "Suggesting that we knew all this before however misses the importance of their study, in which a single experiment provided more information than has been achieved over 15 years of research."

Studying the whole of a genome is getting cheaper and Dr Stephen Bentley, from the Sanger Institute, believes it could change the way we treat illnesses. He told the BBC: "Potentially every time someone is ill we could isolate the genome of a bacterial infection, determine if it is resistant, how it will behave in humans and match it up to a database to monitor the spread of an outbreak."

Writing in Science, Professors Mark Enright and Brian Spratt, reviewed the study: "The ease with which investigators can now obtain whole genomes of bacterial pathogens is opening up a number of questions that previously were impossible or difficult to address. "One of these is how virulent or high drug resistant strains of bacterial pathogens spread within hospitals and nursing homes within a region."
Dr Bentley thinks pathogen genomics could become part of normal hospital practice in five to 10 years' time.

Artificial blood vessels keep in fridge until heart operation

By James Gallagher Health reporter, BBC News

US scientists believe they can produce a ready made supply of blood vessels for use in heart bypass surgery.A study on baboons and dogs in Science Translational Medicine suggests vessels could be stored for up to a year and used by any patient. Blood-carrying tubes can already be grown from a patient's own cells, but this takes several months.

UK experts said the research was exciting.

In coronary heart disease, the arteries which bring oxygen to the heart muscle narrow and become blocked. It is the UK's biggest killer.Every year 28,000 coronary artery bypasses are performed, where blood vessels from other parts of the body are taken and used to "bypass" the blockage. It is not always possible to use the patient's own blood vessels and several research groups are trying to create artificial ones.

"This study shows that bioengineering can be used to create a novel type of vascular graft that has the potential to improve outcomes for patients.” Professor Jeremy Pearson British Heart Foundation

The researchers, at the biotech firm Humacyte, the Brody School of Medicine at East Carolina University and Duke University Medical Centre in North Carolina, built an artificial tube-shaped scaffold and added human smooth muscle cells.As the cells grow they build their own scaffolding out of collagen, and the original structure breaks down.The researchers then used detergent to kill off the cells so the remaining collagen tube could be implanted in anyone without triggering an immune reaction.
The tubes can be stored for a least 12 months and when used in baboons they were still allowing the blood to flow normally after a six month trial. It is the combination of storage and that the blood vessels could be implanted into any patient that has the researchers excited.

They said: "Patients have no waiting period for graft production because the grafts have already been created and stored as opposed to custom made grafts for each patient that involve a lengthy waiting time."
Professor Laura Niklason, cofounder of Humacyte, told the BBC: "I think it really takes regenerative medicine to the next level.""Normally you have to take cells and grow a tissue for one patient at a time, now we can do it on a mass scale, it's a game changer."

Professor John Hunt, UK centre for tissue engineering, said: "It's very exciting you just have to address the safety issues."
"It's a big leap from producing cell-based products for healthy animals for a short time to producing them for unhealthy humans for a lifetime. How do you ensure it lasts for 10 to 15 years, which would be a major advance?"
Professor Jeremy Pearson, associate medical director at the British Heart Foundation, said: "Not everyone is well enough to have a vein taken from another part of their body during heart surgery, so using synthetic veins can become an important part of a patient's treatment. However, sometimes even synthetic veins aren't suitable.
"This study shows that bioengineering can be used to create a novel type of vascular graft that has the potential to improve outcomes for patients. We look forward to the results of clinical trials designed to test this."The method of engineering blood vessel tissue which can be implanted into any patient could have other applications.Professor Niklason said: "It can be used for skin, ligaments, cartilage or other simple tissues where it is really the structure, not the cells, which provide the function."

The researchers hope to begin human trials on artificial blood vessels next year.