Biological Psychology Links

Scientists are closer to understanding what triggers muscle damage in one of the most common forms of muscular dystrophy, called facioscapulohumeral muscular dystrophy (FSHD). FSHD affects about 1 in 20,000 people, and is named for progressive weakness and wasting of muscles in the face, shoulders and upper arms. Although not life-threatening, the disease is disabling. The facial weakness in FSHD, for example, often leads to problems with chewing and speaking. The new research was funded in part by the National Institutes of Health and appears in the journal Science. Until now, there were few clues to the mechanism of FSHD and essentially no leads for potential therapies, beyond symptomatic treatments, said John Porter, Ph.D., a program director at NIH's National Institute of Neurological Disorders and Stroke (NINDS). "This study presents a model of the disease that ties together many complex findings, and will allow researchers to test new theories and potential new treatments," Dr. Porter said. In the early 1990s, researchers found that FSHD is associated with a shortened DNA sequence located on chromosome 4. Experts predicted that discovery of one or more FSHD genes was imminent, but while a handful of candidate genes gradually emerged, none of them were found to have a key role in the disease. The mysteries surrounding FSHD deepened in 2002 when researchers, led by Silvere van der Maarel, Ph.D., at Leiden University in the Netherlands, found that the shortened DNA sequence on chromosome 4 is not enough to cause FSHD. They discovered that the disease occurs only among people who have the shortened DNA sequence plus other sequence variations on chromosome 4. That work was funded in part by NIH, the FSH Society and the Muscular Dystrophy Association.

By Kay Lazar New research suggests that athletes who have had multiple head injuries, and possibly others such as military veterans exposed to repetitive brain traumas, may be prone to developing a disabling neurological disease similar to amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig’s disease. A team of researchers from Boston University School of Medicine and the Veterans Administration Hospital in Bedford said yesterday they have pinpointed evidence of a new disease that mimics ALS in the brains of two former National Football League players previously thought to have died of ALS. They also found the new disease in the brain of a deceased professional boxer who was a military veteran. In most cases, ALS strikes people — many in the prime of life — with no apparent rhyme or reason. The progressive nerve disorder, which affects an estimated 30,000 Americans, slowly paralyzes patients while leaving their mind intact. But if this early research is borne out by autopsies of additional athletes and veterans, it would support the idea that an ALS-type illness can be triggered by the traumas of sports and war. “We believe that these three cases are the tip of the iceberg,’’ said neurosurgeon Robert Cantu, who is a codirector of the BU Center for the Study of Traumatic Encephalopathy. “We don’t know whether this is linked to the increased incidence of ALS in the military, who are subject to blasts and other head injuries, but we are concerned that it may be.’’ The findings, the authors speculated, could mean that athletes and some others previously diagnosed with ALS actually had the related syndrome — perhaps even Gehrig himself, the New York Yankees star who is the iconic ALS sufferer. It’s a mystery that will never be solved, however, because Gehrig’s body was cremated. © 2010 NY Times Co

By Tina Hesman Saey Pumping up is easier for people who have been buff before, and now scientists think they know why — muscles retain a memory of their former fitness even as they wither from lack of use. That memory is stored as DNA-containing nuclei, which proliferate when a muscle is exercised. Contrary to previous thinking, those nuclei aren’t lost when muscles atrophy, researchers report online August 16 in the Proceedings of the National Academy of Sciences. The extra nuclei form a type of muscle memory that allows the muscle to bounce back quickly when retrained. The findings suggest that exercise early in life could help fend off frailness in the elderly, and also raise questions about how long doping athletes should be banned from competition, says study leader Kristian Gundersen, a physiologist at the University of Oslo in Norway. Muscle cells are huge, Gundersen says. And because the cells are so big, more than one nucleus is needed to supply the DNA templates for making large amounts of the proteins that give muscle its strength. Previous research has demonstrated that with exercise, muscle cells get even bigger by merging with stem cells called satellite cells, which are nestled between muscle fiber cells. Researchers had previously thought that when muscles atrophy, the extra nuclei are killed by a cell death program called apoptosis. © Society for Science & the Public 2000 - 2010

The immune system may have a key role in the development of Parkinson's disease, say US researchers. In a 20-year study of 4,000 people, half with Parkinson's disease, the team found an association between genes controlling immunity and the condition. The results raise the possibility of new targets for drug development, Nature Genetics reports. Parkinson's UK said the study strengthened the idea that immunity is an important driver of the disease. The team were not just looking for a genetic cause of the disease, but also considered clinical and environmental factors. During their search, they discovered that groups of genes collectively known as HLA genes are associated with the condition. These genes are key for the immune system to differentiate between foreign invaders and the body's own tissues. In theory, that enables the immune system to attack infectious organisms without turning on itself - but it is not always an infallible system. The genes vary considerably between individuals. Some versions of the genes are associated with increased risk or protection against infectious disease, while others can induce autoimmune disorders in which the immune system attacks the body's own tissues. Inflammation Multiple sclerosis has already been shown to be associated with the same HLA genetic variant seen in the latest study in Parkinson's disease, the researchers said. (C)BBC

By Kay Lazar CHELSEA — Steve Saling talks about being lucky and as happy as he has ever been, which might seem odd, given that Saling cannot speak, walk, or move his hands. His “voice’’ is the monotone of a computer, activated by an infrared beam he moves with almost imperceptible twitches of his head. The 41-year-old former landscape architect has Lou Gehrig’s disease, also known as amyotrophic lateral sclerosis, a progressive nerve disorder that slowly paralyzes patients while leaving their mind intact. They eventually lose the ability to even breathe, often within five years. Saling was diagnosed four years ago, a month after the birth of his son. Instead of despairing, he went into overdrive, determined to use technology to stay one step ahead of the relentless and usually lethal disease. Now he is blazing a path for many others. Through a chance encounter shortly after his diagnosis, he teamed up with Barry Berman, chief executive of the Chelsea Jewish Foundation, and helped to design the nation’s first residence for ALS patients needing nursing care. Using customized infrared technology, patients have far more independence than in a typical nursing home. Saling, who once specialized in making public parks accessible for disabled people, is its first resident. © 2010 NY Times Co.

By Carolyn Y. Johnson In the ever-expanding world of medical devices, early adopters have a new option: a robotic arm. A Cambridge start-up, Myomo Inc., is making an expensive stroke therapy available directly to patients, an effort to encourage use of the novel device. The Myomo arm, based on technology developed at the Massachusetts Institute of Technology, is in many ways a natural extension of research that has shown repetitive-exercise therapy can help stroke patients regain movement. The lightweight prosthesis straps onto the arm and reads signals from the muscles to give a patient an assist when he or she moves the limb. But there is no rigorous scientific evidence demonstrating how well it works. And the $7,000 device casts a spotlight on the hard-to-navigate world of rehabilitation devices — in which patients who are often desperate face a growing number of products whose effectiveness is still being determined. “While there’s some suggestive, tiny studies — that are really pilot studies — that it might be useful, there’s no proof of efficacy using the usual criteria,’’ said Dr. Joel Stein, chairman of the rehabilitation and regenerative medicine department at Columbia University. He is also on Myomo’s scientific advisory board. “I’ve worked with many stroke patients through the years, and I’m careful to not be too paternalistic deciding for them. . . . They feel like the medical system has given up on them, and there’s a fine line between not over-promising and saying we have nothing shown to be helpful, therefore you should just give up.’’ © 2010 NY Times Co

By Katherine Harmon Researchers have been searching for decades for a way to mend damage to the spinal cord, an injury that can lead to life-long paralysis. Even the smallest of breaks in these crucial central nerve fibers can result in the loss of leg, arm and other bodily functions. And attempts to prompt healing, through stem cells or growth factors, have yet to achieve widespread success. Previous research had been stepping closer to encouraging neuronal growth—which usually stops after physical maturation. And a 2008 study coauthored by Zhigang He, a neurologist at Children's Hospital Boston, announced success in shutting down a gene that stops neuron cell growth, thus enticing damaged nerves to start growing again. Through that process, the team was able to reestablish a severed optical nerve connection in mice. A new study, coauthored in part by He and other members of the 2008 team, demonstrates that voluntary movement can be reestablished in mice with spinal cord damage after removing a common enzyme that regulates the neuronal cell growth. The results were published online August 8 in Nature Neuroscience (Scientific American is part of Nature Publishing Group). The removed enzyme PTEN, a phosphatase and tensin homolog, helps to dictate activity in the mTOR pathway, which plays a role in cell growth. During maturation, PTEN is activated, halting cell regeneration, but after removing it from a group of experimental mice with spinal cord injury, the neurons grew as they did in the development phase. © 2010 Scientific American,

By NICHOLAS WADE Two research reports published Friday offer novel approaches to the age-old dream of regenerating the body from its own cells. Animals like newts and zebra fish can regenerate limbs, fins, even part of the heart. If only people could do the same, amputees might grow new limbs and stricken hearts be coaxed to repair themselves. But humans have very little regenerative capacity, probably because of an evolutionary trade-off: suppressing cell growth reduced the risk of cancer, enabling humans to live longer. A person can renew his liver to some extent, and regrow a fingertip while very young, but not much more. In the first of the two new approaches, a research group at Stanford University led by Helen M. Blau, Jason H. Pomerantz and Kostandin V. Pajcini has taken a possible first step toward unlocking the human ability to regenerate. By inactivating two genes that work to suppress tumors, they got mouse muscle cells to revert to a younger state, start dividing and help repair tissue. What is true of mice is often true of humans, and although scientists are a long way from being able to cause limbs to regenerate, the research is attracting attention. Jeremy Brockes, a leading expert on regeneration at University College London, said the report was “an excellent paper.” Though there is a lot still to learn about the process, “it is hard to imagine that it will not be informative for regenerative medicine in the future,” he said. Copyright 2010 The New York Times Company

NEW YORK — Want to maximize the placebo effect? A good way to do this, according to a new study, is to tell someone they have a decent chance of getting the real treatment instead of a fake pill, but keep them guessing. In the study, Parkinson's disease patients given a placebo after being told they had a 75 percent chance of receiving an active drug produced significant amounts of dopamine, a chemical key to the brain's reward system that is scarce in the brains of patients with this disease. But no dopamine response occurred in patients given placebo after being told they had a 25 percent, 50 percent, or 100 percent chance of getting real treatment. The findings show that expectations directly regulate the power of the placebo effect by kicking the brain's reward system into gear, probably not just in Parkinson's patients but in a number of different illnesses, such as chronic pain and depression, according to Dr. A. Jon Stoessl of the Pacific Parkinson's Research Center in Vancouver, British Columbia, and his colleagues. "The greatest form of reward is really to get better, so expectation of improvement is akin to expectation of reward," Stoessl explained in an interview. Stoessl and his colleagues first demonstrated a relationship between the placebo effect and dopamine release in Parkinson's patients nine years ago. Given dopamine's role in the reward system, he explained, "perhaps it would be important for the placebo effect in other conditions." SOURCE: http://link.reuters.com/cab43n Archives of General Psychiatry, August 2010. Copyright 2010 Reuters.

By CLAUDIA DREIFUS About four years ago, John Donoghue’s son, Jacob, then 18, took his father aside and declared, “Dad, I now understand what you do — you’re ‘The Matrix’!” Dr. Donoghue, 61, is a professor of engineering and neuroscience at Brown University, studying how human brain signals could combine with modern electronics to help paralyzed people gain greater control over their environments. He’s designed a machine, the BrainGate, that uses thought to move objects. We spoke for two hours in his Brown University offices in Providence, R.I., and then again by telephone. An edited version of the two conversations follows: Q. WHAT EXACTLY IS BRAINGATE? A. It’s a way for people who’ve been paralyzed by strokes, spinal cord injuries or A.L.S. to connect their brains to the outside world. The system uses a tiny sensor that’s been implanted into the part of a person’s brain that generates movement commands. This sensor picks up brain signals, transmits them to a plug attached to the person’s scalp. The signals then go to a computer which is programmed to translate them into simple actions. Q. WHY MOVE THE SIGNALS OUT OF THE BODY? A. Because for many paralyzed people, there’s been a break between their brain and the rest of their nervous system. Their brains may be fully functional, but their thoughts don’t go anywhere. What BrainGate does is bypass the broken connection. Free of the body, the signal is directed to machines that will turn thoughts into action. Copyright 2010 The New York Times Company

By KENNETH CHANG For caterpillars, what you see on the outside as they crawl is not necessarily what Shaped something like an accordion, the tobacco hornworm caterpillar moves one segment at a time. First, the back legs on the last segment step forward, then the second-to-last segment and so on until finally the front segment with its head moves forward. Researchers at Tufts University and Virginia Tech were curious about the interior biomechanics of this form of movement, so they stuck the caterpillars on a treadmill within a powerful X-ray light source at Argonne National Laboratory in Illinois. For most creatures, including people, the innards and the outer parts are connected to something rigid like a skeleton or carapace, and the movements of the inside and the outside are synchronized. But caterpillars are almost entirely squishy, and the researchers were surprised when they saw that the guts of the caterpillar move differently. “It amazes me and blows my mind that there are still very unusual things to discover about such a humble creature,” said Michael A. Simon, a researcher at Tufts University in Boston who is the lead author of a paper describing the caterpillar locomotion, to be published in the journal Current Biology. Copyright 2010 The New York Times Company

by Dolly J. Krishnaswamy Seven months ago, a 51-year-old woman known only to the public as patient LI1 suffered a severe stroke and lost her ability to communicate with the outside world. She couldn't even blink her eyes. But now, thanks to a new technology, the woman can write long, emotional e-mails to her loved ones just by sniffing. Like many quadriplegics, patient LI1's stroke damaged a region high up on her spinal column, paralyzing her from the neck down. But LI1's injury was so extensive that she also lost the ability to speak. Such patients are referred to as "locked-in" because they can't communicate with the outside world, even though their brain functions normally. Some can blink to answer simple yes or no questions or even string words together by picking out letters as someone recites them (as in the case of Jean-Dominique Bauby, author of The Diving Bell and the Butterfly). But this isn't an option for Patient LI1. So neurobiologist Noam Sobel of the Weizmann Institute of Science in Rehovot, Israel, turned to sniffing. He and colleagues had been studying the human sense of smell and had developed a device, which looks like the oxygen tubes patients wear in the hospital, that releases an odor when a subject sniffs forcefully. Sobel's team soon realized that the device could be configured to respond to various types of sniffing, such as sniffing harder or softer. And that meant it could have applications for locked-in patients. "We thought you could use this sniff to control anything, " Sobel says. "You could even fly a plane." © 2010 American Association for the Advancement of Science.

In humans, throwing a ball, typing on a keyboard, or engaging in most other physical activities involves the coordination of numerous discrete movements that are organized as action sequences. Scientists at the National Institutes of Health and the Gulbenkian Institute in Portugal have identified brain activity in mice that can signal the initiation and termination of newly learned action sequences. The findings appear online today in the current issue of Nature. “This interesting report should advance our understanding of the neurobiology of movement disorders, and open new avenues of research for their treatment and prevention,” says Kenneth R. Warren, Ph.D., acting director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the NIH. The study was conducted by Xin Jin, Ph.D. an investigator in the NIAAA Laboratory for Integrative Neuroscience, and Rui M. Costa, D.V.M, Ph.D., principal investigator of the Champalimaud Neuroscience Program at the Gulbenkian Institute. The researchers trained mice to press a lever exactly eight times to receive a sugar-water reward. As the mice learned this task, the researchers monitored brain cell activity in the animals' basal ganglia, deep brain structures that are known to help start and control movement. “We recorded activity in the dorsal striatum and substantia nigra during the learning of novel action sequences,” explained Dr. Jin. “Although previous studies have reported changes in neural activity in these areas during movement, their role in the initiation and termination of newly learned action sequences has not been explored.”

By NICHOLAS WADE A potentially promising approach to treating Alzheimer’s disease has been developed by researchers studying sirtuin, a protein thought capable of extending lifespan in laboratory animals. Using mice prone to developing Alzheimer’s, the researchers showed that activating sirtuin suppressed the disease and that destroying sirtuin made it much worse. The finding was made by Gizem Donmez, Leonard Guarente and colleagues at the Massachusetts Institute of Technology, who say it raises the hope of treating Alzheimer’s, and possibly other neurodegenerative diseases like Parkinson’s and Huntington’s, with drugs that activate sirtuin. Researchers not involved in the study agreed. “We think it is a scientifically compelling story that ties the sirtuins to the biology of Alzheimer’s disease,” said Dr. Dennis J. Selkoe, an Alzheimer’s expert at Harvard Medical School. But the therapeutic implications, Dr. Selkoe added, “remain quite up in the air.” Another expert, Dr. Juan C. Troncoso of Johns Hopkins University School of Medicine, said the finding “opens a very good avenue, but it’s not without a lot of technical challenges.” Drugs that activate sirtuin already exist, including resveratrol, a minor ingredient of red wine and other foods, and small-molecule chemicals designed to mimic resveratrol. Sirtris, the company that developed the drugs, is testing them against diabetes and other diseases. This generation of drugs does not cross the blood-brain barrier so would not work against Alzheimer’s. Copyright 2010 The New York Times Company

Steve Connor Huntington’s disease is a relatively rare genetic disorder that you wouldn’t wish upon your worst enemy. If you carry a single copy of the affected gene you are destined to die a horrible death involving uncontrollable movements, psychiatric disturbances and progressive dementia. The first symptoms typically occur around the age of 40, and it takes between 10 and 15 more years for the gradual neurodegeneration to end life. Ten years after the excitement of mapping the human genome, and the revolution in the understanding of genetic disorders that the achievement has brought, it is easy to forget that some of those directly affected by inherited diseases have seen little in terms of practical benefit. The gene involved in Huntington’s disease was mapped to chromosome 4 in 1983 by a team led by Jim Gusella at Harvard Medical School in Boston, but it took another 10 years of intensive effort to isolate and clone the gene itself. This allowed scientists to find the type of changes, or mutations, that cause the disorder – the mutated gene has about two or three times the normal number of ‘GAG repeats. I remember on both occasions – in 1983 and 1993 – there were optimistic predictions that the discoveries would soon lead to a test for the carriers of the Huntington’s mutation and effective treatments – even possibly a cure – for the disease. The sad fact is that although a relatively cheap and accurate diagnostic test for the Huntington’s mutation has existed for some years, this medical advance has for the affected families arguably produced more misery than it has eradicated. For a start, there has been no accompanying revolution in treatment, largely because there are so few affected people (estimated to be about 12,000 in Britain) to make it worth the expense and effort of the drug companies to develop new therapies. ©independent.co.uk

Having low vitamin D levels may increase a person's risk of developing Parkinson's disease later in life, say Finnish researchers. Their study of 3,000 people, published in Archives of Neurology, found people with the lowest levels of the sunshine vitamin had a three-fold higher risk. Vitamin D could be helping to protect the nerve cells gradually lost by people with the disease, experts say. The charity Parkinson's UK said further research was required. Parkinson's disease affects several parts of the brain, leading to symptoms like tremor and slow movements. The researchers from Finland's National Institute for Health and Welfare measured vitamin D levels from the study group between 1978 and 1980, using blood samples. They then followed these people over 30 years to see whether they developed Parkinson's disease. They found that people with the lowest levels of vitamin D were three times more likely to develop Parkinson's, compared with the group with the highest levels of vitamin D. Most vitamin D is made by the body when the skin is exposed to sunlight, although some comes from foods like oily fish, milk or cereals. As people age, however, their skin becomes less able to produce vitamin D. Doctors have known for many years that vitamin D helps calcium uptake and bone formation. But research is now showing that it also plays a role in regulating the immune system, as well as in the development of the nervous system. (C)BBC

By GRETCHEN REYNOLDS What goes on inside your brain when you exercise? That question has preoccupied a growing number of scientists in recent years, as well as many of us who exercise. In the late 1990s, Dr. Fred Gage and his colleagues at the Laboratory of Genetics at the Salk Institute in San Diego elegantly proved that human and animal brains produce new brain cells (a process called neurogenesis) and that exercise increases neurogenesis. The brains of mice and rats that were allowed to run on wheels pulsed with vigorous, newly born neurons, and those animals then breezed through mazes and other tests of rodent I.Q., showing that neurogenesis improves thinking. But how, exactly, exercise affects the staggeringly intricate workings of the brain at a cellular level has remained largely mysterious. A number of new studies, though, including work published this month by Mr. Gage and his colleagues, have begun to tease out the specific mechanisms and, in the process, raised new questions about just how exercise remolds the brain. Some of the most reverberant recent studies were performed at Northwestern University’s Feinberg School of Medicine in Chicago. There, scientists have been manipulating the levels of bone-morphogenetic protein or BMP in the brains of laboratory mice. BMP, which is found in tissues throughout the body, affects cellular development in various ways, some of them deleterious. In the brain, BMP has been found to contribute to the control of stem cell divisions. Your brain, you will be pleased to learn, is packed with adult stem cells, which, given the right impetus, divide and differentiate into either additional stem cells or baby neurons. As we age, these stem cells tend to become less responsive. They don’t divide as readily and can slump into a kind of cellular sleep. It’s BMP that acts as the soporific, says Dr. Jack Kessler, the chairman of neurology at Northwestern and senior author of many of the recent studies. The more active BMP and its various signals are in your brain, the more inactive your stem cells become and the less neurogenesis you undergo. Your brain grows slower, less nimble, older. Copyright 2010 The New York Times Company

by Laurie Rich, Jane Bosveld, Andrew Grant, Amy Barth The brain is a castle on a hill. Encased in bone and protected by a special layer of cells, it is shielded from infections and injuries—but also from many pharmaceuticals and even from the body’s own immune defenses. As a result, brain problems are tough to diagnose and to treat. To meet this challenge, researchers are exploring unconventional therapies, from electrodes to laser-light stimulation to mind-bending drugs. Some of these radical experiments may never pan out. But, as frequently happens in medicine, a few of today’s improbable approaches may evolve into tomorrow’s miraculous cures. 1. Man Meets Machine In a sense, cyborgs already walk among us: Nearly 200,000 deaf or near-deaf people have cochlear implants, electronic sound-processing machines that stimulate the auditory nerve and link into the brain. But even by the fanciful science fiction definition, the age of cyborgs is just around the corner. In the last decade, researchers have become increasingly skilled at detecting and interpreting brain signals. Technologies that allow people to use their thoughts to control machines—computers, speaking devices, or prosthetic limbs—are already being tested and could soon be available for widespread applications.

By Stacey Singer Health Writer It would cost $100,000 for the operation that could stop her mother’s tremors. No one in the family had that kind of money, and there was no health insurance. Grace Donofrio knew all this as she scanned the Internet, reading about the latest surgical treatment for tremors caused by Parkinson’s disease. It was early in 2001, and Donofrio, full of hope, called a family meeting. She told her brother and sister that no matter what it cost, no matter what they had to sell or borrow, they must find a way to give their mother the operation. Somberly, they all agreed. In her healthy days, Neponezia Simoes crafted beautiful dresses, an elegant confection of organdy and flowers for Donofrio’s wedding, a variation of Chanel or St. Lauren for a regular customer. Copyright © 2001, South Florida Sun-Sentinel

By Julia Sommerfeld MSNBC DENVER, — Experimental transplants of cells from aborted fetuses and donated eyes are showing promise for the treatment of Parkinson’s disease, according to two studies out Wednesday. Both types of cells were shown to survive in patients’ brains and improve some of the hallmark symptoms of the dreaded disease. PARKINSON’S, which affects an estimated 1 million people in the United States, is caused when the brain cells that produce a chemical known as dopamine die off. Colorado researchers reported follow-up results on a controversial experiment in which holes were drilled in the skull and dopamine cells from aborted fetuses were implanted in the brains of advanced Parkinson’s patients. Other doctors described the initial results of transplants of dopamine cells from the retinas of donated eyes. Both findings were presented at the annual meeting of the American Academy of Neurology in Denver. “It takes the loss of 80 percent to 90 percent of dopamine-producing neurons to lead to the symptoms of Parkinson’s disease,” said Dr. Robin Brey, a professor of medicine, division of neurology at University of Texas Health Sciences Center, San Antonio. “So you need fairly small amount of dopamine-producing neurons to remain normal. That tells us that even if a small number of transplanted cells were to take and produce dopamine, that could do a lot. So this is very promising.” MSNBC Terms, Conditions and Privacy © 2002

Chapter 11. Motor Control and Plasticity