Posts tagged brain cells
Articles and news from the latest research reports.
How Inactivity Changes the Brain
A number of studies have shown that exercise can remodel the brain by prompting the creation of new brain cells and inducing other changes. Now it appears that inactivity, too, can remodel the brain, according to a notable new report.
The study, which was conducted in rats but likely has implications for people too, the researchers say, found that being sedentary changes the shape of certain neurons in ways that significantly affect not just the brain but the heart as well. The findings may help to explain, in part, why a sedentary lifestyle is so bad for us.
Until about 20 years ago, most scientists believed that the brain’s structure was fixed by adulthood, that you couldn’t create new brain cells, alter the shape of those that existed or in any other way change your mind physically after adolescence.
But in the years since, neurological studies have established that the brain retains plasticity, or the capacity to be reshaped, throughout our lifetimes. Exercise appears to be particularly adept at remodeling the brain, studies showed.
But little has been known about whether inactivity likewise alters the structure of the brain and, if so, what the consequences might be.
So for a study recently published in The Journal of Comparative Neurology, scientists at Wayne State University School of Medicine and other institutions gathered a dozen rats. They settled half of them in cages with running wheels and let the animals run at will. Rats like running, and these animals were soon covering about three miles a day on their wheels.
The other rats were housed in cages without wheels and remained sedentary.
Can Fish Oil Help Preserve Brain Cells?
People with higher levels of the omega-3 fatty acids found in fish oil may also have larger brain volumes in old age equivalent to preserving one to two years of brain health, according to a study published in the January 22, 2014, online issue of Neurology®, the medical journal of the American Academy of Neurology. Shrinking brain volume is a sign of Alzheimer’s disease as well as normal aging.
For the study, the levels of omega-3 fatty acids EPA+DHA in red blood cells were tested in 1,111 women who were part of the Women’s Health Initiative Memory Study. Eight years later, when the women were an average age of 78, MRI scans were taken to measure their brain volume.
Those with higher levels of omega-3s had larger total brain volumes eight years later. Those with twice as high levels of fatty acids (7.5 vs. 3.4 percent) had a 0.7 percent larger brain volume.
“These higher levels of fatty acids can be achieved through diet and the use of supplements, and the results suggest that the effect on brain volume is the equivalent of delaying the normal loss of brain cells that comes with aging by one to two years,” said study author James V. Pottala, PhD, of the University of South Dakota in Sioux Falls and Health Diagnostic Laboratory, Inc., in Richmond, Va.
Those with higher levels of omega-3s also had a 2.7 percent larger volume in the hippocampus area of the brain, which plays an important role in memory. In Alzheimer’s disease, the hippocampus begins to atrophy even before symptoms appear.
How metabolism and brain activity are linked
A new study by scientists at McGill University and the University of Zurich shows a direct link between metabolism in brain cells and their ability to signal information. The research may explain why the seizures of many epilepsy patients can be controlled by a specially formulated diet.
(Image caption: Neurons in the cerebellum. Credit: Bowie Lab/McGill University)
The findings, published Jan. 16 in Nature Communications, reveal that metabolism controls the processes that inhibit brain activity, such as that involved in convulsions. The study uncovers a link between how brain cells make energy and how the same cells signal information – processes that neuroscientists have often assumed to be distinct and separate.
“Inhibition in the brain is commonly targeted in clinical practice,” notes Derek Bowie, Canada Research Chair in Receptor Pharmacology at McGill and corresponding author of the study. “For example, drugs that alleviate anxiety, induce anesthesia, or even control epilepsy work by strengthening brain inhibition. These pharmacological approaches can have their drawbacks, since patients often complain of unpleasant side effects.”
The experiments showed an unexpected link between how the mitochondria of brain cells make energy and how the same cells signal information. Brain cells couple these two independent functions by using small chemical messengers, called reactive oxygen species (or ROS), that are normally associated with signaling cell death. While ROS are known to have roles in diseases of aging, such as Alzheimer’s and Parkinson’s, the new study shows they also play important roles in the healthy brain.
The findings emerged from an ongoing collaboration between Prof. Bowie’s laboratory in McGill’s Department of Pharmacology and Therapeutics and a research team headed by Dr. Jean-Marc Fritschy, Professor of Pharmacology at the University of Zurich and current director of the Neuroscience Center Zurich (ZNZ). The researchers have the longer term aim of trying to understand why the seizures of many epilepsy patients — especially young children – can be treated with a high-fat, low-carbohydrate diet known as the ketogenic diet.
The idea that diet can control seizures was noticed as far back as ancient Greece, during periods of fasting. From the 1920s until the 1950s, the ketogenic diet was widely used to treat epilepsy patients. With the introduction of anticonvulsant drugs in the 1950s, the dietary approach fell out of favour with doctors. But because anticonvulsant drugs don’t work for 20% to 30% of patients, there has been a resurgence in use of the ketogenic diet.
“Since our study shows that brain cells have their own means to strengthen inhibition,” explains Prof Bowie, “our work points to potentially new ways in which to control a number of important neurological conditions including epilepsy.”
(Source: mcgill.ca)
Breast cancer spreads to brain by masquerading as neurons
Often, several years can pass between the time a breast cancer patient successfully goes into remission and a related brain tumor develops. During that time, the breast cancer cells somehow hide, escaping detection as they grow and develop. Now City of Hope researchers have found out how.
Breast cancer cells disguise themselves as neurons, becoming “cellular chameleons,” the scientists found. This allows them to slip undetected into the brain and, from there, develop into tumors.
The discovery is being heralded as “a tremendous advance in breast cancer research.”
Although breast cancer is a very curable disease – with more than 95 percent of women with early-stage disease surviving after five years – breast cancer that metastasizes to the brain is difficult to fight. In fact, only about 20 percent of patients survive a year after diagnosis.
"There remains a paucity of public awareness about cancer’s relentless endgame," said Rahul Jandial, M.D., Ph.D., a City of Hope neurosurgeon who headed the breast-cancer-and-brain-tumor study, published online ahead of print this week in the Proceedings of the National Academy of Sciences.
"Cancer kills by spreading. In fact, 90 percent of all cancer mortality is from metastasis," Jandial said. "The most dreaded location for cancer to spread is the brain. As we have become better at keeping cancer at bay with drugs such as Herceptin, women are fortunately living longer. In this hard-fought life extension, brain metastases are being unmasked as the next battleground for extending the lives of women with breast cancer."
He added: “I have personally seen my neurosurgery clinic undergo a sharp rise in women with brain metastases years – and even decades – after their initial diagnosis.”
Jandial and other City of Hope scientists wanted to explore how breast cancer cells cross the blood-brain barrier – a separation of the blood circulating in the body from fluid in the brain – without being destroyed by the immune system.
“If, by chance, a malignant breast cancer cell swimming in the bloodstream crossed into the brain, how would it survive in a completely new, foreign habitat?” said Jandial in a recent interview with New Scientist.
Jandial and his team’s hypothesis: Given that the brain is rich in many brain-specific types of chemicals and proteins, perhaps breast cancer cells that could exploit these resources by assuming similar properties would be the most likely to flourish. These cancer cells could deceive the immune system by blending in with the neurons, neurotransmitters, other types of proteins, cells and chemicals.
Taking samples from brain tumors resulting from breast cancer, Jandial and his team found that the breast cancer cells were exploiting the brain’s most abundant chemical as a fuel source. This chemical, GABA, is a neurotransmitter used for communication between neurons.
When compared to cells from nonmetastatic breast cancer, the metastasized cells expressed a receptor for GABA, as well as for a protein that draws the transmitter into cells. This allowed the cancer cells to essentially masquerade as neurons.”Breast cancer cells can be cellular chameleons (or masquerade as neurons) and spread to the brain,” Jandial said.
Jandial says that further study is required to better understand the mechanisms that allow the cancer cells to achieve this disguise. He hopes that ultimately, unmasking these disguised invaders will result in new therapies.
Turning off major memory switch dulls memories
A faultily formed memory sounds like hitting random notes on a keyboard while a proper one sounds more like a song, scientists say.
When they turned off a major switch for learning and memory, brain cells communicated, but the relationship was superficial, said Dr. Joe Tsien, neuroscientist at the Medical College of Georgia at Georgia Regents University and Co-Director of the GRU Brain & Behavior Discovery Institute.
“We have begun to crack the neural code, which allows us to look in real time at how thoughts happen and how memories are made,” Tsien said. “That has enabled us to understand for the first time how and whether the right keys are struck at the right time and in the right place and manner to make the beautiful sound of coherent memories and to compare what happens when a key element is missing.”
With the NMDA receptor intact, chatter reverberates, associations are made and helpful memories – like how touching a hot stove results in a burn – are easily retrieved.
“You see a face and think of a name, you see your office, and you think you need to work; everything is associative,” said Tsien, corresponding author of the study in the journal PLOS ONE. “But in mice lacking an NMDA receptor, you can tell the memory patterns are dull and dissociated.”
Using the century-old Pavlovian conditioning model that first showed how repetition creates association, they found that mice lacking a functioning NMDA receptor in the hippocampus, the brain’s center of learning and memory, could not recollect even something fearful.
When they played a tone, followed 20 seconds later by a mild foot shock, normal mice quickly made the association, down to the timing. The connection essentially never registered with mice lacking the NMDA receptor. Healthy brain recalling memories and Amnesic brain recalling contextual memories
“They form the initial patterns, but don’t rehearse them,” said Tsien. “Their tones are flat, the association is poor, while everything we register in the healthy brain is associative.” To illustrate just how flat, Postdoctoral Fellow Hui Kuang assigned musical notes to the memory activity of each, which resulted in random noise by the NMDA knockout mice compared to a dynamic rhythm from normal mice.
“By knowing what these patterns look like and what they mean, you can use this signature to measure, for example, during aging, why we begin to lose memory and to identify and test drugs that are truly effective at aiding memory,” Tsien said.
“You can tell whether there is an issue with reverberation, whether your brain is repeating what you need to remember, or repeats it but somehow stores it badly, so it’s not associated with the right things. This study has revealed a lot of fascinating details about what neuroscientists call the brain’s neural code” Tsien said.”
He wants to look at how aging affects these processes as a next step. The research team also is looking at Doogie, a mouse genetically bred by Tsien and his team in 1999 to be exceptionally smart, to see if they can also learn more about how super memories are made and what they look like.
This ability to decode how and what the brain is remembering, should one day help physicians better assess and treat conditions such as Alzheimer’s and schizophrenia, Tsien said. They may find that some answers are already out there, such as drugs that boost reverberation, or a stimulant like caffeine to help retrieve a memory, Tsien said.
His team first reported decoding brain cell conversations as memories were formed and recalled in PLOS ONE in 2009. As with the new study, they used a computational algorithm to translate the neuronal conversations into some of the first pictures of what memories look like.
Gene Found To Be Crucial For Formation Of Certain Brain Circuitry
Using a powerful gene-hunting technique for the first time in mammalian brain cells, researchers at Johns Hopkins report they have identified a gene involved in building the circuitry that relays signals through the brain. The gene is a likely player in the aging process in the brain, the researchers say. Additionally, in demonstrating the usefulness of the new method, the discovery paves the way for faster progress toward identifying genes involved in complex mental illnesses such as autism and schizophrenia — as well as potential drugs for such conditions. A summary of the study appears in the Dec. 12 issue of Cell Reports.
(Image: A mouse neuron with synapses shown: Red dots mark excitatory synapses, while green dots mark so-called inhibitory synapses. Credit: Kamal Sharma/Johns Hopkins University School of Medicine)
“We have been looking for a way to sift through large numbers of genes at the same time to see whether they affect processes we’re interested in,” says Richard Huganir, Ph.D., director of the Johns Hopkins University Solomon H. Snyder Department of Neuroscience and a Howard Hughes Medical Institute investigator, who led the study. “By adapting an automated process to neurons, we were able to go through 800 genes to find one needed for forming synapses — connections — among those cells.”
Although automated gene-sifting techniques have been used in other areas of biology, Huganir notes, many neuroscience studies instead build on existing knowledge to form a hypothesis about an individual gene’s role in the brain. Traditionally, researchers then disable or “knock out” the gene in lab-grown cells or animals to test their hypothesis, a time-consuming and laborious process.
In this study, Huganir’s group worked to test many genes all at once using plastic plates with dozens of small wells. A robot was used to add precise allotments of cells and nutrients to each well, along with molecules designed to knock out one of the cells’ genes — a different one for each well.
“The big challenge was getting the neurons, which are very sensitive, to function under these automated conditions,” says Kamal Sharma, Ph.D., a research associate in Huganir’s group. The team used a trial-and-error approach, adjusting how often the nutrient solution was changed and adding a washing step, and eventually coaxed the cells to thrive in the wells. In addition, Sharma says, they fine-tuned an automated microscope used to take pictures of the circuitry that had formed in the wells and calculated the numbers of synapses formed among the cells.
The team screened 800 genes in this way and found big differences in the well of cells with a gene called LRP6 knocked out. LRP6 had previously been identified as a player in a biochemical chain of events known as the Wnt pathway, which controls a range of processes in the brain. Interestingly, Sharma says, the team found that LRP6 was only found on a specific kind of synapse known as an excitatory synapse, suggesting that it enables the Wnt pathway to tailor its effects to just one synapse type.
“Changes in excitatory synapses are associated with aging, and changes in the Wnt pathway in later life may accelerate aging in general. However, we do not know what changes take place in the synaptic landscape of the aging brain. Our findings raise intriguing questions: Is the Wnt pathway changing that landscape, and if so, how?” says Sharma. “We’re interested in learning more about what other proteins LRP6 interacts with, as well as how it acts in different types of brain cells at different developmental stages of circuit development and refinement.”
Another likely outcome of the study is wider use of the gene-sifting technique, he says, to explore the genetics of complex mental illnesses. The automated method could also be used to easily test the effects on brain cells of a range of molecules and see which might be drug candidates.
Broken cellular ‘clock’ linked to brain damage
A new discovery may help explain the surprisingly strong connections between sleep problems and neurodegenerative conditions such as Alzheimer’s disease. Sleep loss increases the risk of Alzheimer’s disease, and disrupted sleeping patterns are among the first signs of this devastating disorder.
Scientists at Washington University School of Medicine in St. Louis and the University of Pennsylvania have shown that brain cell damage similar to that seen in Alzheimer’s disease and other disorders results when a gene that controls the sleep-wake cycle and other bodily rhythms is disabled.
The researchers found evidence that disabling a circadian clock gene that controls the daily rhythms of many bodily processes blocks a part of the brain’s housekeeping cycle that neutralizes dangerous chemicals known as free radicals.
“Normally in the hours leading up to midday, the brain increases its production of certain antioxidant enzymes, which help clean up free radicals,” said first author Erik Musiek, MD, PhD, assistant professor of neurology at the School of Medicine. “When clock genes are disabled, though, this surge no longer occurs, and the free radicals may linger in the brain and cause more damage.”
Musiek conducted the research in the labs of Garret FitzGerald, MD, chairman of pharmacology at the University of Pennsylvania, and of David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology at Washington University School of Medicine, who are co-senior authors.
The study appears Nov. 25 in The Journal of Clinical Investigation.
Musiek studied mice lacking a master clock gene called Bmal1. Without this gene, activities that normally occur at particular times of day are disrupted.
“For example, mice normally are active at night and asleep during the day, but when Bmal1 is missing, they sleep equally in the day and in the night, with no circadian rhythm,” Musiek said. “They get the same amount of sleep, but it’s spread over the whole day. Rhythms in the way genes are expressed are lost.”
FitzGerald uses mice lacking Bmal1 to study whether clock cells have links to diabetes and heart disease. He has shown that clock genes influence blood pressure, blood sugar and lipid levels.
Several years ago, Musiek, who at the time was a neurology resident at the University of Pennsylvania, and FitzGerald decided to investigate how knocking out Bmal1 affects the brain. Holtzman, who has published pioneering work on sleep and Alzheimer’s disease, encouraged Musiek to continue and expand these studies when he came to Washington University as a postdoctoral fellow.
In the new study, Musiek found that as the mice aged, many of their brain cells became damaged and did not function normally. The patterns of damage were similar to those seen in Alzheimer’s disease and other neurodegenerative disorders.
“Brain cell injury in these mice far exceeded that normally seen in aging mice,” Musiek said. “Many of the injuries appear to be caused by free radicals, which are byproducts of metabolism. If free radicals come into contact with brain cells or other tissue, they can cause damaging chemical reactions.”
This led Musiek to examine the production of key antioxidant enzymes, which usually neutralize and help clear free radicals from the brain, thereby limiting damage. He found levels of several antioxidant proteins peak in the middle of the day in healthy mice. However, this surge is absent in mice lacking Bmal1. Without the surge, free radicals may remain in the brain longer, contributing to the damage Musiek observed.
“We’re trying to identify more specifics about how problems in clock genes contribute to neurodegeneration, both with and without influencing sleep,” Musiek said. “That’s a challenging distinction to make, but it needs to be made because clock genes appear to control many other functions in the brain in addition to sleeping and waking.”
(Source: news.wustl.edu)
Scientists identify protein responsible for controlling communication between brain cells
Scientists are a step closer to understanding how some of the brain’s 100 billion nerve cells co-ordinate their communication. The study is published in the journal Cell Reports.
The University of Bristol research team investigated some of the chemical processes that underpin how brain cells co-ordinate their communication. Defects in this communication are associated with disorders such as epilepsy, autism and schizophrenia, and therefore these findings could lead to the development of novel neurological therapies.
Neurons in the brain communicate with each other using chemicals called neurotransmitters. This release of neurotransmitter from neurons is tightly controlled by many different proteins inside the neuron. These proteins interact with each other to ensure that neurotransmitter is only released when necessary. Although the mechanisms that control this release have been extensively studied, the processes that co-ordinate how and when the component proteins interact is not fully understood.
The School of Biochemistry researchers have now discovered that one of these proteins called ‘RIM1α’ is modified by a small protein named ‘SUMO’ which attaches to a specific region in RIM1α. This process acts as a ‘molecular switch’ which is required for normal neurotransmitter release.
Jeremy Henley, Professor of Molecular Neuroscience in the University’s Faculty of Medical and Veterinary Sciences and the study’s lead author, said: “These findings are important as they show that SUMO modification plays a vital and previously unsuspected role in normal brain function.”
The research builds on the team’s earlier work that identified a group of proteins in the brain responsible for protecting nerve cells from damage and could be used in future for therapies for stroke and other brain diseases.
(Source: bristol.ac.uk)
Nicotine withdrawal traced to very specific group of brain cells
Nicotine withdrawal might take over your body, but it doesn’t take over your brain. The symptoms of nicotine withdrawal are driven by a very specific group of neurons within a very specific brain region, according to a report in Current Biology, a Cell Press publication, on November 14. Although caution is warranted, the researchers say, the findings in mice suggest that therapies directed at this group of neurons might one day help people quit smoking.
(Image: Fotolia)
"We were surprised to find that one population of neurons within a single brain region could actually control physical nicotine withdrawal behaviors," says Andrew Tapper of the Brudnick Neuropsychiatric Research Institute at the University of Massachusetts Medical School.
Tapper and his colleagues first obtained mice addicted to nicotine by delivering the drug to mice in their water for a period of 6 weeks. Then they took the nicotine away. The mice started scratching and shaking in the way a dog does when it is wet. Close examination of the animals’ brains revealed abnormally increased activity in neurons within a single region known as the interpeduncular nucleus.
When the researchers artificially activated those neurons with light, animals showed behaviors that looked like nicotine withdrawal, whether they had been exposed to the drug or not. The reverse was also true: treatments that lowered activity in those neurons alleviated nicotine withdrawal symptoms.
That the interpeduncular nucleus might play such a role in withdrawal from nicotine makes sense because the region receives connections from other areas of the brain involved in nicotine use and response, as well as feelings of anxiety. The interpeduncular nucleus is also densely packed with nicotinic acetylcholine receptors that are the molecular targets of nicotine.
It is much less clear whether the findings related to nicotine will be relevant to other forms of addiction, but there are some hints that they may.
"Smoking is highly prevalent in people with other substance-use disorders, suggesting a potential interaction between nicotine and other drugs of abuse," Tapper says. "In addition, naturally occurring mutations in genes encoding the nicotinic receptor subunits that are found in the interpeduncular nucleus have been associated with drug and alcohol dependence."
(Source: eurekalert.org)
Scientists shed light on the brain mechanisms behind a debilitating sleep disorder
Researchers at the University of Toronto discover how the body’s muscles accidentally fall asleep while awake
Normally muscles contract in order to support the body, but in a rare condition known as cataplexy the body’s muscles “fall asleep” and become involuntarily paralyzed. Cataplexy is incapacitating because it leaves the affected individual awake, but either fully or partially paralyzed. It is one of the bizarre symptoms of the sleep disorder called narcolepsy.
“Cataplexy is characterized by muscle paralysis during cognitive awareness, but we didn’t understand how this happened until now, said John Peever of the University of Toronto’s Department of Cell & Systems Biology. “We have shown that the neuro-degeneration of the brain cells that synthesize the chemical hypocretin causes the noradrenaline system to malfunction. When the norandrenaline system stops working properly, it fails to keep the motor and cognitive systems coupled. This results in cataplexy – the muscles fall asleep but the brain stays awake.”
Peever and Christian Burgess, also of Cell & Systems Biology used hypocretin-knockout mice (mice that experience cataplexy), to demonstate that a dysfunctional relationship between the noradrenaline system and the hypocretin-producing system is behind cataplexy. The research was recently published in the journal Current Biology.
The scientists first established that mice experienced sudden loss of muscle tone during cataplectic episodes. They then administered drugs to systematically inhibit or activate a particular subset of adrenergic receptors, the targets of noradrenaline. They were able to reduce the incidence of cataplexy by 90 per cent by activating noradrenaline receptors. In contrast, they found that inhibiting the same receptors increased the incidence of cataplexy by 92 per cent. Their next step was to successfully link how these changes affect the brain cells that directly control muscles.
They found that noradrenaline is responsible for keeping the brain cells (motoneurons) and muscles active. But during cataplexy when muscle tone falls, noradrenaline levels disappear. This forces the muscle to relax and causes paralysis during cataplexy. Peever and Burgess found that restoring noradrenaline pre-empted cataplexy, confirming that the noradrenaline system plays a key role.
(Source: media.utoronto.ca)