Category: Neurology

New research shows that drug for Parkinson’s disease (benztropine) may also treat multiple sclerosis

On By A.P.In benztropine, cogentin, fingolimod, interferon beta, MS, multiple sclerosis, myelin, Nature, Neurology, Neuropsychiatric Disease, Neuropsychopharmacology, Neuroscience, oligodendrocyte, Parkinson's diseaseLeave a comment

benzotropine

A drug that treats Parkinson’s disease might also work against multiple sclerosis, or MS.

In MS patients, an aberrant immune onslaught degrades the fatty myelin sheaths that coat nerve fibers, causing blurred vision, weakness, loss of coordination and other symptoms.

Luke Lairson of the Scripps Research Institute in La Jolla, Calif., and colleagues tested a host of compounds to see which might boost regeneration of oligodendrocytes, the brain cells that make myelin and which are often lacking in MS. Using the cells’ forerunners, nascent brain cells called oligodendrocyte precursor cells, from rats and mice, the researchers found that benztropine proved adept at steering these cells to become myelin-making oligodendrocytes.

The researchers then induced in mice a disease that mimics MS and gave some of the animals benztropine, others a standard MS drug (fingolimod or interferon beta) and some no drug at all. Whether given before or after disease onset, benztropine reduced symptom severity and prevented relapses better than other MS drugs. Mice getting no drug fared the poorest, according to results appearing October 9 in Nature.

A cell count of brain tissue revealed that mice getting benztropine had substantially more mature oligodendrocytes than mice getting no drug. Further analyses suggested the animals’ symptom improvement with benztropine resulted from a rebuilding of the myelin sheaths, not from suppressing the animals’ immune systems. The researchers think the drug, if approved for use in MS, might work in concert with immune-suppressing drugs.

Old drug may have new trick

How Exercise Beefs Up the Brain

On By A.P.In Alzheimer's disease, Barbara Hempstead, BDNF, Boston, brain derived neurotrophic factor, brown fat, Bruce Spiegelman, Cell Metabolism, Christiane Wrann, Dementia, diabetes, Dr. Rajadhyaksha, Exercise, FNDC5, Harvard Medical School, hippocampus, irisin, Karolinska Institute in Sweden, Medicine, Nature, neurologist, Neurology, Neuropsychiatric Disease, Neuroscience, neuroscientist, neurotrophin, Obesity, Parkinson's disease, PGC-1α, Pontus Boström, Science, The Brain, Weill Cornell Medical College, white fatLeave a comment

exercise

New research explains how abstract benefits of exercise—from reversing depression to fighting cognitive decline—might arise from a group of key molecules.

While our muscles pump iron, our cells pump out something else: molecules that help maintain a healthy brain. But scientists have struggled to account for the well-known mental benefits of exercise, from counteracting depression and aging to fighting Alzheimer’s and Parkinson’s disease. Now, a research team may have finally found a molecular link between a workout and a healthy brain.

Much exercise research focuses on the parts of our body that do the heavy lifting. Muscle cells ramp up production of a protein called FNDC5 during a workout. A fragment of this protein, known as irisin, gets lopped off and released into the bloodstream, where it drives the formation of brown fat cells, thought to protect against diseases such as diabetes and obesity. (White fat cells are traditionally the villains.)

While studying the effects of FNDC5 in muscles, cellular biologist Bruce Spiegelman of Harvard Medical School in Boston happened upon some startling results: Mice that did not produce a so-called co-activator of FNDC5 production, known as PGC-1α, were hyperactive and had tiny holes in certain parts of their brains. Other studies showed that FNDC5 and PGC-1α are present in the brain, not just the muscles, and that both might play a role in the development of neurons.

Spiegelman and his colleagues suspected that FNDC5 (and the irisin created from it) was responsible for exercise-induced benefits to the brain—in particular, increased levels of a crucial protein called brain-derived neurotrophic factor (BDNF), which is essential for maintaining healthy neurons and creating new ones. These functions are crucial to staving off neurological diseases, including Alzheimer’s and Parkinson’s. And the link between exercise and BDNF is widely accepted. “The phenomenon has been established over the course of, easily, the last decade,” says neuroscientist Barbara Hempstead of Weill Cornell Medical College in New York City, who was not involved in the new work. “It’s just, we didn’t understand the mechanism.”

To sort out that mechanism, Spiegelman and his colleagues performed a series of experiments in living mice and cultured mouse brain cells. First, they put mice on a 30-day endurance training regimen. They didn’t have to coerce their subjects, because running is part of a mouse’s natural foraging behavior. “It’s harder to get them to lift weights,” Spiegelman notes. The mice with access to a running wheel ran the equivalent of a 5K every night.

Aside from physical differences between wheel-trained mice and sedentary ones—“they just look a little bit more like a couch potato,” says co-author Christiane Wrann, also of Harvard Medical School, of the latter’s plumper figures—the groups also showed neurological differences. The runners had more FNDC5 in their hippocampus, an area of the brain responsible for learning and memory.

Using mouse brain cells developing in a dish, the group next showed that increasing the levels of the co-activator PGC-1α boosts FNDC5 production, which in turn drives BDNF genes to produce more of the vital neuron-forming BDNF protein. They report these results online today in Cell Metabolism. Spiegelman says it was surprising to find that the molecular process in neurons mirrors what happens in muscles as we exercise. “What was weird is the same pathway is induced in the brain,” he says, “and as you know, with exercise, the brain does not move.”

So how is the brain getting the signal to make BDNF? Some have theorized that neural activity during exercise (as we coordinate our body movements, for example) accounts for changes in the brain. But it’s also possible that factors outside the brain, like those proteins secreted from muscle cells, are the driving force. To test whether irisin created elsewhere in the body can still drive BDNF production in the brain, the group injected a virus into the mouse’s bloodstream that causes the liver to produce and secrete elevated levels of irisin. They saw the same effect as in exercise: increased BDNF levels in the hippocampus. This suggests that irisin could be capable of passing the blood-brain barrier, or that it regulates some other (unknown) molecule that crosses into the brain, Spiegelman says.

Hempstead calls the findings “very exciting,” and believes this research finally begins to explain how exercise relates to BDNF and other so-called neurotrophins that keep the brain healthy. “I think it answers the question that most of us have posed in our own heads for many years.”

The effect of liver-produced irisin on the brain is a “pretty cool and somewhat surprising finding,” says Pontus Boström, a diabetes researcher at the Karolinska Institute in Sweden. But Boström, who was among the first scientists to identify irisin in muscle tissue, says the work doesn’t answer a fundamental question: How much of exercise’s BDNF-promoting effects come from irisin reaching the brain from muscle cells via the bloodstream, and how much are from irisin created in the brain?

Though the authors point out that other important regulator proteins likely play a role in driving BDNF and other brain-nourishing factors, they are focusing on the benefits of irisin and hope to develop an injectable form of FNDC5 as a potential treatment for neurological diseases and to improve brain health with aging.

http://news.sciencemag.org/biology/2013/10/how-exercise-beefs-brain

Thanks to Dr. Rajadhyaksha for bringing this to the attention of the It’s Interesting community.

After cardiac arrest, a final surge of brain activity could contain vivid experience, new research in rodents suggests.

On By A.P.In Allen Institute for Brain Science, brain, cardiac arrest, Christof Koch, death, EEG, electroencephalography, Jimo Borjigin, Kebmodee, near-death experiences, Neurology, Neuron, Neuroscience, neuroscientist, Proceedings of the National Academy of Sciences, Sam Parnia, Science, University of Michigan1 Comment

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What people experience as death creeps in—after the heart stops and the brain becomes starved of oxygen—seems to lie beyond the reach of science. But the authors of a new study on dying rats make a bold claim: After cardiac arrest, the rodents’ brains enter a state similar to heightened consciousness in humans. The researchers suggest that if the same is true for people, such brain activity could be the source of the visions and other sensations that make up so-called near-death experiences.

Estimated to occur in about 20% of patients who survive cardiac arrest, near-death experiences are frequently described as hypervivid or “realer-than-real,” and often include leaving the body and observing oneself from outside, or seeing a bright light. The similarities between these reports are hard to ignore, but the conversation about near-death experiences often bleeds into metaphysics: Are these visions produced solely by the brain, or are they a glimpse at an afterlife outside the body?

Neurologist Jimo Borjigin of the University of Michigan, Ann Arbor, got interested in near-death experiences during a different project—measuring the hormone levels in the brains of rodents after a stroke. Some of the animals in her lab died unexpectedly, and her measurements captured a surge in neurochemicals at the moment of their death. Previous research in rodents and humans has shown that electrical activity surges in the brain right after the heart stops, then goes flat after a few seconds. Without any evidence that this final blip contains meaningful brain activity, Borjigin says “it’s perhaps natural for people to assume that [near-death] experiences came from elsewhere, from more supernatural sources.” But after seeing those neurochemical surges in her animals, she wondered about those last few seconds, hypothesizing that even experiences seeming to stretch for days in a person’s memory could originate from a brief “knee-jerk reaction” of the dying brain.

To observe brains on the brink of death, Borjigin and her colleagues implanted electrodes into the brains of nine rats to measure electrical activity at six different locations. The team anesthetized the rats for about an hour, for ethical reasons, and then injected potassium chloride into each unconscious animal’s heart to cause cardiac arrest. In the approximately 30 seconds between a rat’s last heartbeat and the point when its brain stopped producing signals, the team carefully recorded its neuronal oscillations, or the frequency with which brain cells were firing their electrical signals.

The data produced by electroencephalograms (EEGs) of the nine rats revealed a highly organized brain response in the seconds after cardiac arrest, Borjigin and colleagues report online today in the Proceedings of the National Academy of Sciences. While overall electrical activity in the brain sharply declined after the last heartbeat, oscillations in the low gamma frequency (between 25 and 55 Hz) increased in power. Previous human research has linked gamma waves to waking consciousness, meditative states, and REM sleep. These oscillations in the dying rats were synchronized across different parts of the brain, even more so than in the rat’s normal waking state. The team also noticed that firing patterns in the front of the brain would be echoed in the back and sides. This so-called top-down signaling, which is associated with conscious perception and information processing, increased eightfold compared with the waking state, the team reports. When you put these features together, Borjigin says, they suggest that the dying brain is hyperactive in its final seconds, producing meaningful, conscious activity.

The team proposed that such research offers a “scientific framework” for approaching the highly lucid experiences that some people report after their brushes with death. But relating signs of consciousness in rat brains to human near-death experiences is controversial. “It opens more questions than it answers,” says Christof Koch, a neuroscientist at the Allen Institute for Brain Science in Seattle, Washington, of the research. Evidence of a highly organized and connected brain state during the animal’s death throes is surprising and fascinating, he says. But Koch, who worked with Francis Crick in the early 1980s to hypothesize that gamma waves are a hallmark of consciousness, says the increase in their frequency doesn’t necessarily mean that the rats were in a hyperconscious state. Not only is it impossible to project any mental experience onto these animals, but their response was also “still overlaid by the anesthesiology,” he says; this sedation likely influenced their brain response in unpredictable ways.

Others share Koch’s concerns. “There is no animal model of a near-death experience,” says critical care physician Sam Parnia of Stony Brook University School of Medicine in New York. We can never confirm what animals think or feel in their final moments, making it all but impossible to use them to study our own near-death experiences, he believes. Nonetheless, Parnia sees value in this new study from a clinical perspective, as a step toward understanding how the brain behaves right before death. He says that doctors might use a similar approach to learn how to improve blood flow or prolong electrical activity in the brain, preventing damage while resuscitating a patient.

Borjigin argues that the rat data are compelling enough to drive further study of near-death experiences in humans. She suggests monitoring EEG activity in people undergoing brain surgery that involves cooling the brain and reducing its blood supply. This procedure has prompted near-death experiences in the past, she says, and could offer a systematic way to explore the phenomenon.

read more here: http://news.sciencemag.org/brain-behavior/2013/08/probing-brain%E2%80%99s-final-moments

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.

People in their 90s are getting smarter

On By A.P.In aged brain, aging, Danish Aging Research Center, Kaare Christensen, Marcel Olde Rikkert, mini-mental state examination, Netherlands, Neurology, nonagenarian, Radboud University Nijmegen Medical Centre, The Lancet, University of Southern Denmark in OdenseLeave a comment

happyoldman

Ninety-somethings seem to be getting smarter. Today’s oldest people are surviving longer, and thankfully appear to have sharper minds than the people reaching their 90s 10 years ago.

Kaare Christensen, head of the Danish Aging Research Center at the University of Southern Denmark in Odense, and colleagues found Danish people born in 1915 were about a third more likely to live to their 90s than those born in 1905, and were smarter too.

During research, which spanned 12 years and involved more than 5000 people, the team gave nonagenarians born in 1905 and 1915 a standard test called a “mini-mental state examination”, and cognitive tests designed to pick up age-related changes. Not only did those born in 1915 do better at both sets of tests, more of them also scored top marks in the mini-mental state exam.

It’s a landmark study, says Marcel Olde Rikkert, head of the Alzheimer’s centre at Radboud University Nijmegen Medical Centre in the Netherlands. It is scientifically rigorous, it invited all over 90-year-olds in Denmark to participate, and it also overturns our ingrained views of old age, he says.

“The outcome underlines that ageing is malleable,” Olde Rikkert says, adding that cognitive function can actually be a lot better than people would assume until a very high age.

“It’s motivating that people, their lifestyles, and their environments can contribute a lot to the way they age,” he says, though he cautions that not everything is in our own hands and help is still needed for those with dementia or those who do experience cognitive decline as they age.

Improved education played a part in the changes, says Christensen. But the study does not disentangle the individual effects of the numerous things that could be responsible for the improvements. “The 1915 cohort had a number of factors on their side – they experienced better living and working conditions, they had radio, TV and newspapers earlier in their lives than those born 10 years before,” he says.

Tellingly, there was no difference in the physical test results between the two groups. The authors say this “suggests changes in the intellectual environment rather than in the physical environment are the basis for the improvement”.

Journal reference: The Lancet, DOI: 10.1016/S0140-6736(13)60777-1

http://www.newscientist.com/article/dn23864-people-in-their-90s-are-getting-smarter.html?cmpid=RSS|NSNS|2012-GLOBAL|online-news#.UeE-56UTPfY

Brain stimulation at any age may slow memory decline

On By A.P.In brain, chess, cognitive reserve, memory, Neurology, Neuroscience, photography, quilting, reading, Robert Wilson, Rush University Medical Center, writingLeave a comment

reading

It’s never too early to start protecting your brain power, a new study suggests.

Reading, writing and participating in other brain-stimulating activities at any age may protect your memory later in life, according to the research. The study, which tracked 294 individuals, is published online in the July 3 issue of Neurology.

“Our study suggests that exercising your brain by taking part in activities such as these across a person’s lifetime, from childhood through old age, is important for brain health in old age,” said the study’s lead author, Robert Wilson.

After adjusting for signs of brain disease, higher levels of cognitive activity across the life span were associated with slower cognitive decline, the study found. Mental activity explained about 14% of the differences between people in how much their memory and thinking skills declined.

The finding supports the hypothesis of cognitive reserve, which describes the brain’s ability to cope with disease or damage. According to the hypothesis, mental activity helps delay the cognitive consequences of disease.

Neuroimaging research suggests that cognitive activity can lead to changes in brain structure and function that may enhance cognitive reserve.

“An intellectually stimulating lifestyle helps to contribute to cognitive reserve and allows you to tolerate these age-related brain pathologies better than someone who has had a less cognitively active lifestyle,” says Wilson, a neuropsychologist at Rush University Medical Center in Chicago.

He recommends that people have cognitively stimulating hobbies that they enjoy, such as photography and quilting.

Intellectually stimulating activities involve processing and using information. Examples are reading a book and then predicting what will happen next, as well as watching a movie and then comparing it with other films, says Judy Willis, a neurologist based in Santa Barbara, Calif.

Willis says doing a variety of cognitive activities appears to be more protective of the cognitive reserve than focusing on one thing, even something like playing chess. “More research is needed to look at how much time should be devoted to an activity or learning a skill and how often it should be revisited,” she adds.

Willis, who was not involved in the study, agrees that the activities should be motivated by pleasure. “Forcing yourself to do something takes a lot of mental effort,” she adds. “If you try something and don’t like it, try something else.”

http://www.usatoday.com/story/news/nation/2013/07/03/brain-aging-activities/2461655/

Brain implants: Restoring memory with a microchip

On By A.P.In brain, brain computer interface, Constantine Lyketsos, Doug Brown, hippocampus, Inventions, Johnny Mnemonic, memory, neural activity, neural prosthetics, Neurology, neuroplasticity, neuroprosthetic device, Neuroscience, neuroscientist, neurosurgery, Rob Hampson, Science, Technology, Ted Berger, The Brain, The Future, The Singularity, University of Southern California, Wake Forest University1 Comment

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William Gibson’s popular science fiction tale “Johnny Mnemonic” foresaw sensitive information being carried by microchips in the brain by 2021. A team of American neuroscientists could be making this fantasy world a reality. Their motivation is different but the outcome would be somewhat similar. Hailed as one of 2013’s top ten technological breakthroughs by MIT, the work by the University of Southern California, North Carolina’s Wake Forest University and other partners has actually spanned a decade.

But the U.S.-wide team now thinks that it will see a memory device being implanted in a small number of human volunteers within two years and available to patients in five to 10 years. They can’t quite contain their excitement. “I never thought I’d see this in my lifetime,” said Ted Berger, professor of biomedical engineering at the University of Southern California in Los Angeles. “I might not benefit from it myself but my kids will.”

Rob Hampson, associate professor of physiology and pharmacology at Wake Forest University, agrees. “We keep pushing forward, every time I put an estimate on it, it gets shorter and shorter.”

The scientists — who bring varied skills to the table, including mathematical modeling and psychiatry — believe they have cracked how long-term memories are made, stored and retrieved and how to replicate this process in brains that are damaged, particularly by stroke or localized injury.

Berger said they record a memory being made, in an undamaged area of the brain, then use that data to predict what a damaged area “downstream” should be doing. Electrodes are then used to stimulate the damaged area to replicate the action of the undamaged cells.

They concentrate on the hippocampus — part of the cerebral cortex which sits deep in the brain — where short-term memories become long-term ones. Berger has looked at how electrical signals travel through neurons there to form those long-term memories and has used his expertise in mathematical modeling to mimic these movements using electronics.

Hampson, whose university has done much of the animal studies, adds: “We support and reinforce the signal in the hippocampus but we are moving forward with the idea that if you can study enough of the inputs and outputs to replace the function of the hippocampus, you can bypass the hippocampus.”

The team’s experiments on rats and monkeys have shown that certain brain functions can be replaced with signals via electrodes. You would think that the work of then creating an implant for people and getting such a thing approved would be a Herculean task, but think again.

For 15 years, people have been having brain implants to provide deep brain stimulation to treat epilepsy and Parkinson’s disease — a reported 80,000 people have now had such devices placed in their brains. So many of the hurdles have already been overcome — particularly the “yuck factor” and the fear factor.

“It’s now commonly accepted that humans will have electrodes put in them — it’s done for epilepsy, deep brain stimulation, (that has made it) easier for investigative research, it’s much more acceptable now than five to 10 years ago,” Hampson says.

Much of the work that remains now is in shrinking down the electronics.

“Right now it’s not a device, it’s a fair amount of equipment,”Hampson says. “We’re probably looking at devices in the five to 10 year range for human patients.”

The ultimate goal in memory research would be to treat Alzheimer’s Disease but unlike in stroke or localized brain injury, Alzheimer’s tends to affect many parts of the brain, especially in its later stages, making these implants a less likely option any time soon.

Berger foresees a future, however, where drugs and implants could be used together to treat early dementia. Drugs could be used to enhance the action of cells that surround the most damaged areas, and the team’s memory implant could be used to replace a lot of the lost cells in the center of the damaged area. “I think the best strategy is going to involve both drugs and devices,” he says.

Unfortunately, the team found that its method can’t help patients with advanced dementia.

“When looking at a patient with mild memory loss, there’s probably enough residual signal to work with, but not when there’s significant memory loss,” Hampson said.

Constantine Lyketsos, professor of psychiatry and behavioral sciences at John Hopkins Medicine in Baltimore which is trialing a deep brain stimulator implant for Alzheimer’s patients was a little skeptical of the other team’s claims.

“The brain has a lot of redundancy, it can function pretty well if loses one or two parts. But memory involves circuits diffusely dispersed throughout the brain so it’s hard to envision.” However, he added that it was more likely to be successful in helping victims of stroke or localized brain injury as indeed its makers are aiming to do.

The UK’s Alzheimer’s Society is cautiously optimistic.

“Finding ways to combat symptoms caused by changes in the brain is an ongoing battle for researchers. An implant like this one is an interesting avenue to explore,” said Doug Brown, director of research and development.

Hampson says the team’s breakthrough is “like the difference between a cane, to help you walk, and a prosthetic limb — it’s two different approaches.”

It will still take time for many people to accept their findings and their claims, he says, but they don’t expect to have a shortage of volunteers stepping forward to try their implant — the project is partly funded by the U.S. military which is looking for help with battlefield injuries.

There are U.S. soldiers coming back from operations with brain trauma and a neurologist at DARPA (the Defense Advanced Research Projects Agency) is asking “what can you do for my boys?” Hampson says.

“That’s what it’s all about.”

http://www.cnn.com/2013/05/07/tech/brain-memory-implants-humans/index.html?iref=allsearch

Rare brain condition makes woman see everything upside down

On By A.P.In Blic, Bojana Danilovic, Medicine, Neurology, Neuroscience, Science, spatial orientation phenomenon, The BrainLeave a comment

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Bojana Danilovic has what you might call a unique worldview. Due to a rare condition, she sees everything upside down, all the time.

The 28-year-old Serbian council employee uses an upside down monitor at work and relaxes at home in front of an upside down television stacked on top of the normal one that the rest of her family watches.

“It may look incredible to other people but to me it’s completely normal,” Danilovic told local newspaper Blic.

“I was born that way. It’s just the way I see the world.”

Experts from Harvard University and the Massachusetts Institute of Technology have been consulted after local doctors were flummoxed by the extremely unusual condition.

They say she is suffering from a neurological syndrome called “spatial orientation phenomenon,” Blic reports.

“They say my eyes see the images the right way up but my brain changes them,” Danilovic said.

“But they don’t really seem to know exactly how it happens, just that it does and where it happens in my brain.

“They told me they’ve seen the case histories of some people who write the way I see, but never someone quite like me.”

http://au.news.yahoo.com/thewest/a/-/world/16375095/rare-brain-condition-leaves-woman-seeing-world-upside-down/