Category: Neuroscience

‘Jumping Genes’ Linked to Schizophrenia

On By A.P.In DNA, Dr. Rajadhyaksha, gene, Japan, jumping gene, line element, Medicine, mental health, mental illness, neural activity, neurogenesis, neurologist, Neurology, Neuron, neuroplasticity, Neuropsychiatric Disease, Neuroscience, neuroscientist, neurotransmitter, RIKEN Brain Science Institute, schizophrenia, Science, Tadafumi KatoLeave a comment

sn-schizophrenia

Roaming bits of DNA that can relocate and proliferate throughout the genome, called “jumping genes,” may contribute to schizophrenia, a new study suggests. These rogue genetic elements pepper the brain tissue of deceased people with the disorder and multiply in response to stressful events, such as infection during pregnancy, which increase the risk of the disease. The study could help explain how genes and environment work together to produce the complex disorder and may even point to ways of lowering the risk of the disease, researchers say.

Schizophrenia causes hallucinations, delusions, and a host of other cognitive problems, and afflicts roughly 1% of all people. It runs in families—a person whose twin sibling has the disorder, for example, has a roughly 50-50 chance of developing it. Scientists have struggled to define which genes are most important to developing the disease, however; each individual gene associated with the disorder confers only modest risk. Environmental factors such as viral infections before birth have also been shown to increase risk of developing schizophrenia, but how and whether these exposures work together with genes to skew brain development and produce the disease is still unclear, says Tadafumi Kato, a neuroscientist at the RIKEN Brain Science Institute in Wako City, Japan and co-author of the new study.

Over the past several years, a new mechanism for genetic mutation has attracted considerable interest from researchers studying neurological disorders, Kato says. Informally called jumping genes, these bits of DNA can replicate and insert themselves into other regions of the genome, where they either lie silent, doing nothing; start churning out their own genetic products; or alter the activity of their neighboring genes. If that sounds potentially dangerous, it is: Such genes are often the culprits behind tumor-causing mutations and have been implicated in several neurological diseases. However, jumping genes also make up nearly half the current human genome, suggesting that humans owe much of our identity to their audacious leaps.

Recent research by neuroscientist Fred Gage and colleagues at the University of California (UC), San Diego, has shown that one of the most common types of jumping gene in people, called L1, is particularly abundant in human stem cells in the brain that ultimately differentiate into neurons and plays an important role in regulating neuronal development and proliferation. Although Gage and colleagues have found that increased L1 is associated with mental disorders such as Rett syndrome, a form of autism, and a neurological motor disease called Louis-Bar syndrome, “no one had looked very carefully” to see if the gene might also contribute to schizophrenia, he says.

To investigate that question, principal investigator Kazuya Iwamoto, a neuroscientist; Kato; and their team at RIKEN extracted brain tissue of deceased people who had been diagnosed with schizophrenia as well as several other mental disorders, extracted DNA from their neurons, and compared it with that of healthy people. Compared with controls, there was a 1.1-fold increase in L1 in the tissue of people with schizophrenia, as well as slightly less elevated levels in people with other mental disorders such as major depression, the team reports today in Neuron.

Next, the scientists tested whether environmental factors associated with schizophrenia could trigger a comparable increase in L1. They injected pregnant mice with a chemical that simulates viral infection and found that their offspring did, indeed, show higher levels of the gene in their brain tissue. An additional study in infant macaques, which mimicked exposure to a hormone also associated with increased schizophrenia risk, produced similar results. Finally, the group examined human neural stem cells extracted from people with schizophrenia and found that these, too, showed higher levels of L1.

The fact that it is possible to increase the number of copies of L1 in the mouse and macaque brains using established environmental triggers for schizophrenia shows that such genetic mutations in the brain may be preventable if such exposures can be avoided, Kato says. He says he hopes that the “new view” that environmental factors can trigger or deter genetic changes involved in the disease will help remove some of the disorder’s stigma.

Combined with previous studies on other disorders, the new study suggests that L1 genes are indeed more active in the brain of patients with neuropsychiatric diseases, Gage says. He cautions, however, that no one yet knows whether they are actually causing the disease. “Now that we have multiple confirmations of this occurring in humans with different diseases, the next step is to determine if possible what role, if any, they play.”

One tantalizing possibility is that as these restless bits of DNA drift throughout the genomes of human brain cells, they help create the vibrant cognitive diversity that helps humans as a species respond to changing environmental conditions, and produces extraordinary “outliers,” including innovators and geniuses such as Picasso, says UC San Diego neuroscientist Alysson Muotri. The price of such rich diversity may be that mutations contributing to mental disorders such as schizophrenia sometimes emerge. Figuring out what these jumping genes truly do in the human brain is the “next frontier” for understanding complex mental disorders, he says. “This is only the tip of the iceberg.”

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

http://news.sciencemag.org/biology/2014/01/jumping-genes-linked-schizophrenia

Alexandra Wolff: 1 of 55 people in the U.S. with highly superior autobiographical memory.

On By A.P.In Alexandra Wolff, brain, Depression, highly superior autobiographical memory, HSAM, memory, Neurology, Neuropsychiatric Disease, NeuroscienceLeave a comment

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On Feb. 21, Alexandra Wolff ate steak, mashed potatoes and broccoli for dinner. Later that night, sitting in her room, she spent 20 minutes scanning pictures in InStyle magazine.

She remembers those things, just as she remembers that on Aug. 2 she stopped at Target and bought Raisin Bran; and on April 17 she wore a white button-down shirt; and on Oct. 2 she went to TGI Fridays and spoke to the hostess, who was wearing black leather flats with small bows on them.

Alexandra Wolff has what’s known as highly superior autobiographical memory. She is one of only 55 people in the U.S. who have been identified with this ability. All of these people can remember details about their lives that the rest of us couldn’t hope to remember: the strangers they pass on the street, the first thing they saw when they woke up seven months ago.

And though it’s not clear why the brains of people with HSAM can do what they do, what is clear is that this ability gives them an access to the past that’s profoundly different from you and me.

If you think of 2013, probably only a handful of memories stand out. The day-by-day is a blur.

We forget most of our lives.

But Alexandra says that remembering even an inconsequential trip to Target is an almost physical experience for her. She says she sees what she saw that day, hears what she heard, and emotionally feels what she felt at the time.

“Right down to getting sick to my stomach or getting a headache,” she says. “It’s almost like time travel.”

But being unable to forget can affect your relationship to the present, people with this form of memory say.

Alexandra is 22 and lives with her mother in a long brick ranch house in southern Maryland. She has dark hair and beautifully balanced features, but hasn’t really dated and seems to have few of the preoccupations of most 22-year-olds. She blames her memory for this, saying it separates her from other people her age because they can’t understand why she’s so focused on things that have already happened.

Alexandra often feels frustrated with her preoccupation with the past. “It seems like you hold onto everything, and it seems like you’re just stuck in the past all the time,” she says.

It really bothers her. For one, Alexandra says, in her life there are no fresh days, no clean slates without association. Every morning when she wakes up, details of that date from years before are scrolling through her mind, details that can profoundly affect the new day she’s in.

For example, the day before we spoke was a day when years ago in middle school a boy bullied her in one of her classes.

“I didn’t mention it to anyone,” she says, “but I mean, still in the back of my mind I kept thinking and thinking about it. It knocked some of my confidence down.”

Because the past is so viscerally right there, so available, she finds that when the present gets overwhelming, it’s hard not to retreat to the past.

Even though she’s only 22, she says she spends huge amounts of time in her room with her eyes closed, reliving the past in her mind, particularly this one day a decade ago.

It was July 8, 2004. She spent that day in a bathing suit by a pool laughing and playing with her 10-year-old cousin. They ate macaroni and cheese, and swam. It was an easy, innocent time.

She says she probably takes herself through that day in her mind four times a week. Over the past couple of years, she estimates, she’s probably spent close to 2,000 hours reliving that one day.

“I mean, I definitely say it’s a huge temptation. I could, if I didn’t have stuff to do all day, I could probably live in the past 24/7.”
Scientists think there’s a reason why we forget.

“It has long been believed by research scientists that forgetting is adaptive,” says James McGaugh, the University of California, Irvine neurobiologist who first documented highly superior autobiographical memory.

McGaugh discovered HSAM by accident. He got an email out of the blue from a woman named Jill Price who said she had a serious memory problem: She couldn’t seem to forget anything, and like Alexandra, this bothered her.

“The emotions evoked by remembering bad things troubled her,” McGaugh says.

And so McGaugh started studying first Price and then other people with this kind of memory. He found ultimately that there are differences in the brains of people with HSAM, though it’s not clear whether the differences are the cause or the consequence of this ability.

But it is clear that it’s specifically this issue of forgetting that’s different. If you were asked to recall what happened to you earlier this morning, you’d remember roughly the same amount as someone like Alexandra. But if asked about this morning three months from now, for you it would probably be gone, while for her it’s as fresh as it is for you today.

“So it’s not that they’re superior learners,” McGaugh says, “it’s that they are very poor at forgetting.”
The emotional effects of not being able to forget aren’t clear, says McGaugh. No one, including McGaugh, has studied it. His sense is that there is variation in the group of 55.

“The effects of having this ability depends on the kind of experiences people have had in the past as well as their present circumstances,” he says.

But Bill Brown, another person with HSAM, says that he’s been in touch with most of the people in the group, and that everyone he has spoken to has struggled with depression. He says that very few of them have been able to maintain a long-term marriage — the rumor is only 2 out of the 55.
Brown himself, though a pretty jolly guy, recently separated from his wife.

And talking to him, you do get the sense that the difference in his memory has led to misunderstandings in his relationships.

“Just because I remember something that you did wrong doesn’t mean that I still hold it against you,” he says. “But it’s taken me a long while to realize that folks without my ability probably don’t understand that distinction. Because after all, if you’re bringing it up, the logic from the other side would be: You must still hold it against me.”

This is not, in fact, the case, he says. “It has more to do with wanting you to be honest in your dealings.”

What he eventually realized was that most of the people he talks to are being as honest as they know how to be. “They just don’t necessarily remember.”
Brown says it’s easier for him now, because over time he’s learned how to manage the memories, not to focus on the bad stuff, and instead use his memory to entertain himself.

“But you know,” he says, “life’s rough, and there’s so much bad that’s kinda there.”

Sometimes, he says, he thinks it might be nice to forget.

http://www.npr.org/blogs/health/2013/12/18/255285479/when-memories-never-fade-the-past-can-poison-the-present

Could Pot Help Veterans With PTSD? Brain Scientists Say Maybe

On By A.P.In Andrew Holmes, anxiety circuitry, Atlanta, brain, cannabinoids, cannabis, Cannabis sativa, Drugs, Emory University, Emory University School of Medicine, extinction therapy, fear circuitry, Georgia, Jon Hamilton, Kerry Ressler, marijuana, Medicine, military, National Institute of Mental Health, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, Neuropsychiatric Disease, Neuroscience, neuroscientist, post-traumatic stress disorder, pot, psychiatrist, Psychiatry, psychology, psychotherapy, PTSD, Science, tetrahydrocannabinol, THC, VeteransLeave a comment

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by Jon Hamilton

Veterans who smoke marijuana to cope with post-traumatic stress disorder may be onto something. There’s growing evidence that pot can affect brain circuits involved in PTSD.

Experiments in animals show that tetrahydrocannabinol, the chemical that gives marijuana its feel-good qualities, acts on a system in the brain that is “critical for fear and anxiety modulation,” says Andrew Holmes, a researcher at the National Institute on Alcohol Abuse and Alcoholism. But he and other brain scientists caution that marijuana has serious drawbacks as a potential treatment for PTSD.

The use of marijuana for PTSD has gained national attention in the past few years as thousands of traumatized veterans who fought in Iraq and Afghanistan have asked the federal government to give them access to the drug. Also, Maine and a handful of other states have passed laws giving people with PTSD access to medical marijuana.

But there’s never been a rigorous scientific study to find out whether marijuana actually helps people with PTSD. So lawmakers and veterans groups have relied on anecdotes from people with the disorder and new research on how both pot and PTSD works in the brain.

An Overactive Fear System

When a typical person encounters something scary, the brain’s fear system goes into overdrive, says Dr. Kerry Ressler of Emory University. The heart pounds, muscles tighten. Then, once the danger is past, everything goes back to normal, he says.

But Ressler says that’s not what happens in the brain of someone with PTSD. “One way of thinking about PTSD is an overactivation of the fear system that can’t be inhibited, can’t be normally modulated,” he says.

For decades, researchers have suspected that marijuana might help people with PTSD by quieting an overactive fear system. But they didn’t understand how this might work until 2002, when scientists in Germany published a mouse study showing that the brain uses chemicals called cannabinoids to modulate the fear system, Ressler says.

There are two common sources of cannabinoids. One is the brain itself, which uses the chemicals to regulate a variety of brain cells. The other common source is Cannabis sativa, the marijuana plant.

So in recent years, researchers have done lots of experiments that involved treating traumatized mice with the active ingredient in pot, tetrahydrocannabinol (THC), Ressler says. And in general, he says, the mice who get THC look “less anxious, more calm, you know, many of the things that you might imagine.”

Problems with Pot

Unfortunately, THC’s effect on fear doesn’t seem to last, Ressler says, because prolonged exposure seems to make brain cells less sensitive to the chemical.

Another downside to using marijuana for PTSD is side effects, says Andrew Holmes at the National Institute on Alcohol Abuse and Alcoholism. “You may indeed get a reduction in anxiety,” Holmes says. “But you’re also going to get all of these unwanted effects,” including short-term memory loss, increased appetite and impaired motor skills.

So for several years now, Holmes and other scientists have been testing drugs that appear to work like marijuana, but with fewer drawbacks. Some of the most promising drugs amplify the effect of the brain’s own cannabinoids, which are called endocannabinoids, he says. “What’s encouraging about the effects of these endocannabinoid-acting drugs is that they may allow for long-term reductions in anxiety, in other words weeks if not months.”

The drugs work well in mice, Holmes says. But tests in people are just beginning and will take years to complete. In the meantime, researchers are learning more about how marijuana and THC affect the fear system in people.

At least one team has had success giving a single dose of THC to people during something called extinction therapy. The therapy is designed to teach the brain to stop reacting to something that previously triggered a fearful response.

The team’s study found that people who got THC during the therapy had “long-lasting reductions in anxiety, very similar to what we were seeing in our animal models,” Holmes says. So THC may be most useful when used for a short time in combination with other therapy, he says.

As studies continue to suggest that marijuana can help people with PTSD, it may be unrealistic to expect people with the disorder to wait for something better than marijuana and THC, Ressler says. “I’m a pragmatist,” he says. “I think if there are medications including drugs like marijuana that can be used in the right way, there’s an opportunity there, potentially.”

http://www.npr.org/blogs/health/2013/12/23/256610483/could-pot-help-veterans-with-ptsd-brain-scientists-say-maybe

Electric brain stimulation in a specific area discovered to induce a sense of determination

On By A.P.In aMCC, anterior midcingulate cortex, brain, Depression, determination, epilepsy, Josef Parvizi, Kebmodee, motivation, neural activity, neural prosthetics, neurologist, Neurology, Neuron, neuroplasticity, neuroprosthetic device, Neuropsychiatric Disease, Neuropsychopharmacology, Neuroscience, neuroscientist, neurosurgeon, neurosurgery, neurotransmitter, neurotrophin, Stanford, The FutureLeave a comment

Doctors in the US have induced feelings of intense determination in two men by stimulating a part of their brains with gentle electric currents.

The men were having a routine procedure to locate regions in their brains that caused epileptic seizures when they felt their heart rates rise, a sense of foreboding, and an overwhelming desire to persevere against a looming hardship.

The remarkable findings could help researchers develop treatments for depression and other disorders where people are debilitated by a lack of motivation.

One patient said the feeling was like driving a car into a raging storm. When his brain was stimulated, he sensed a shaking in his chest and a surge in his pulse. In six trials, he felt the same sensations time and again.

Comparing the feelings to a frantic drive towards a storm, the patient said: “You’re only halfway there and you have no other way to turn around and go back, you have to keep going forward.”

When asked by doctors to elaborate on whether the feeling was good or bad, he said: “It was more of a positive thing, like push harder, push harder, push harder to try and get through this.”

A second patient had similar feelings when his brain was stimulated in the same region, called the anterior midcingulate cortex (aMCC). He felt worried that something terrible was about to happen, but knew he had to fight and not give up, according to a case study in the journal Neuron.

Both men were having an exploratory procedure to find the focal point in their brains that caused them to suffer epileptic fits. In the procedure, doctors sink fine electrodes deep into different parts of the brain and stimulate them with tiny electrical currents until the patient senses the “aura” that precedes a seizure. Often, seizures can be treated by removing tissue from this part of the brain.

“In the very first patient this was something very unexpected, and we didn’t report it,” said Josef Parvizi at Stanford University in California. But then I was doing functional mapping on the second patient and he suddenly experienced a very similar thing.”

“Its extraordinary that two individuals with very different past experiences respond in a similar way to one or two seconds of very low intensity electricity delivered to the same area of their brain. These patients are normal individuals, they have their IQ, they have their jobs. We are not reporting these findings in sick brains,” Parvizi said.

The men were stimulated with between two and eight milliamps of electrical current, but in tests the doctors administered sham stimulation too. In the sham tests, they told the patients they were about to stimulate the brain, but had switched off the electical supply. In these cases, the men reported no changes to their feelings. The sensation was only induced in a small area of the brain, and vanished when doctors implanted electrodes just five millimetres away.

Parvizi said a crucial follow-up experiment will be to test whether stimulation of the brain region really makes people more determined, or simply creates the sensation of perseverance. If future studies replicate the findings, stimulation of the brain region – perhaps without the need for brain-penetrating electrodes – could be used to help people with severe depression.

The anterior midcingulate cortex seems to be important in helping us select responses and make decisions in light of the feedback we get. Brent Vogt, a neurobiologist at Boston University, said patients with chronic pain and obsessive-compulsive disorder have already been treated by destroying part of the aMCC. “Why not stimulate it? If this would enhance relieving depression, for example, let’s go,” he said.

http://www.theguardian.com/science/2013/dec/05/determination-electrical-brain-stimulation

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

New research shows that sleep functions to allow the brain to eliminate toxins that accumulate while we are awake

On By A.P.In Alzheimer's disease, beta amyloid, brain, brain cleaning, Kebmodee, Maiken Nedergaard, Medicine, mental concentration, mental health, mental illness, National Institute of Neurological Disorders and Stroke, neurologist, Neurology, Neuropsychiatric Disease, Neuroscience, NINDS, Randall Bateman, Science, University of Rochester, Washington UniversityLeave a comment

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While the brain sleeps, it clears out harmful toxins, a process that may reduce the risk of Alzheimer’s, researchers say.

During sleep, the flow of cerebrospinal fluid in the brain increases dramatically, washing away harmful waste proteins that build up between brain cells during waking hours, a study of mice found.

“It’s like a dishwasher,” says Dr. Maiken Nedergaard, a professor of neurosurgery at the University of Rochester and an author of the study in Science.

The results appear to offer the best explanation yet of why animals and people need sleep. If this proves to be true in humans as well, it could help explain a mysterious association between sleep disorders and brain diseases, including Alzheimer’s.

Nedergaard and a team of scientists discovered the cleaning process while studying the brains of sleeping mice. The scientists noticed that during sleep, the system that circulates cerebrospinal fluid through the brain and nervous system was “pumping fluid into the brain and removing fluid from the brain in a very rapid pace,” Nedergaard says.

The team discovered that this increased flow was possible in part because when mice went to sleep, their brain cells actually shrank, making it easier for fluid to circulate. When an animal woke up, the brain cells enlarged again and the flow between cells slowed to a trickle. “It’s almost like opening and closing a faucet,” Nedergaard says. “It’s that dramatic.”

Nedergaard’s team, which is funded by the National Institute of Neurological Disorders and Stroke, had previously shown that this fluid was carrying away waste products that build up in the spaces between brain cells.

The process is important because what’s getting washed away during sleep are waste proteins that are toxic to brain cells, Nedergaard says. This could explain why we don’t think clearly after a sleepless night and why a prolonged lack of sleep can actually kill an animal or a person, she says.

So why doesn’t the brain do this sort of housekeeping all the time? Nedergaard thinks it’s because cleaning takes a lot of energy. “It’s probably not possible for the brain to both clean itself and at the same time [be] aware of the surroundings and talk and move and so on,” she says.

The brain-cleaning process has been observed in rats and baboons, but not yet in humans, Nedergaard says. Even so, it could offer a new way of understanding human brain diseases including Alzheimer’s. That’s because one of the waste products removed from the brain during sleep is beta amyloid, the substance that forms sticky plaques associated with the disease.

That’s probably not a coincidence, Nedergaard says. “Isn’t it interesting that Alzheimer’s and all other diseases associated with dementia, they are linked to sleep disorders,” she says.

Researchers who study Alzheimer’s say Nedergaard’s research could help explain a number of recent findings related to sleep. One of these involves how sleep affects levels of beta amyloid, says Randall Bateman, a professor of neurology Washington University in St. Louis who wasn’t involved in the study.

“Beta amyloid concentrations continue to increase while a person is awake,” Bateman says. “And then after people go to sleep that concentration of beta amyloid decreases. This report provides a beautiful mechanism by which this may be happening.”

The report also offers a tantalizing hint of a new approach to Alzheimer’s prevention, Bateman says. “It does raise the possibility that one might be able to actually control sleep in a way to improve the clearance of beta amyloid and help prevent amyloidosis that we think can lead to Alzheimer’s disease.”

http://www.npr.org/blogs/health/2013/10/17/236211811/brains-sweep-themselves-clean-of-toxins-during-sleep

http://m.sciencemag.org/content/342/6156/373.abstract

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

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

sn-brain

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.

New research on adult neurogenesis shows that about 1,400 new brain cells are born every day, and about 80% of human brain cells in the dentate gyrus of the hippocampus undergo renewal in adulthood

On By A.P.In 14C, adult neurogenesis, atomic bomb, brain, Cell, DNA, hippocampus, Kebmodee, Leonie Welberg, Nature, Nature Neuroscience, Neuron, NeuroscienceLeave a comment

ooold-neurons

bomb

by Leonie Welberg

The question of whether adult neurogenesis occurs in the human hippocampus has been a hotly debated topic in neuroscience. In a study published in Cell, Frisén and colleagues now settle the debate by providing evidence that around 1,400 dentate gyrus cells are born in the human brain every day.

The authors made use of a birth-dating method that is based on the principle that 14C in the atmosphere is taken up by plants and — because humans eat plants and animals that eat plants — eventually also by humans. As 14C is incorporated into DNA during cell division, the 14C content of a cell is thought to reflect 14C levels in the atmosphere at the time of the birth of the cell. Importantly, atomic bomb testing in the 1950s and 1960s resulted in a spike in atmospheric 14C levels, and levels declined after 1963; this means that the level of 14C in cellular DNA can be used as a relatively precise marker of a cell’s birth date.

The authors applied the 14C birth-dating method to whole hippocampi dissected from post-mortem brains donated by individuals who were born in different years in the twentieth century. They separated neurons from non-neuronal hippocampal cells, purified the neuronal DNA and determined 14C levels. Neuronal 14C levels did not match atmospheric 14C levels in the individual’s birth year but were either higher (for people born before 1950) or lower (for people born after 1963), suggesting that at least some of the hippocampal cells were born after the year in which an individual was born.

Computer modelling of the data revealed that the best-fit model was one in which 35% of hippocampal cells showed such turnover, whereas the majority did not (that is, they were born during development). Assuming that, in humans, adult neurogenesis would take place in the dentate gyrus rather than in other hippocampal areas (as it does in rodents), and as the dentate gyrus contains about 44% of all hippocampal neurons, this model suggests that about 80% of human dentate gyrus cells undergo renewal in adulthood. This is in striking contrast to the scenario in mice, in which only ~10% of adult dentate gyrus neurons undergo renewal. The study further showed that there is very little decline in the level of hippocampal neurogenesis with ageing in humans, which is again in contrast to rodents.

It is now well established that adult-born neurons have a functional role in the mouse and rat dentate gyrus and olfactory bulb. A previous study using the same neuronal birth-dating method established that no adult neurogenesis takes place in the olfactory bulb and cortex in humans, but the new study has elegantly shown that the situation is different in the dentate gyrus. Whether the adult-born neurons have functional implications in humans remains a topic for future investigation.

http://www.nature.com/nrn/journal/v14/n8/full/nrn3548.html?WT.ec_id=NRN-201308

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

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/