Posts tagged brain cells
Articles and news from the latest research reports.
Brain adds cells in puberty to navigate adult world
The brain adds new cells during puberty to help navigate the complex social world of adulthood, two Michigan State University neuroscientists report in the current issue of the Proceedings of the National Academy of Sciences.
Scientists used to think the brain cells you’re born with are all you get. After studies revealed the birth of new brain cells in adults, conventional wisdom held that such growth was limited to two brain regions associated with memory and smell.
But in the past few years, researchers in MSU’s neuroscience program have shown that mammalian brains also add cells during puberty in the amygdala and interconnected regions where it was thought no new growth occurred. The amygdala plays an important role in helping the brain make sense of social cues. For hamsters, it picks up signals transmitted by smell through pheromones; in humans, the amygdala evaluates facial expressions and body language.
“These regions are important for social behaviors, particularly mating behavior,” said lead author Maggie Mohr, a doctoral student in neuroscience. “So, we thought maybe cells that are added to those parts of the brain during puberty could be important for adult reproductive function.”
To test that idea, Mohr and Cheryl Sisk, MSU professor of psychology, injected male hamsters with a chemical marker to show cell birth during puberty. When the hamsters matured into adults, the researchers allowed them to interact and mate with females.
Examining the brains immediately after that rendezvous, the researchers found new cells born during puberty had been added to the amygdala and associated regions. Some of the new cells contained a protein that indicates cell activation, which told Mohr and Sisk those cells had become part of the neural networks involved in social and sexual behavior.
“Before this study it was unclear if cells born during puberty even survived into adulthood,” Mohr said. “We’ve shown that they can mature to become part of the brain circuitry that underlies adult behavior.”
Their results also showed that more of the new brain cells survived and became functional in males raised in an enriched environment – a larger cage with a running wheel, nesting materials and other features – than in those with a plain cage.
While people act in more complicated ways than rodents, the researchers said they hope their work ultimately sheds light on human behavior.
“We don’t know if cells are added to the human amygdala during puberty,” Sisk said, “but we know the amygdala plays a similar role in people as in hamsters. We hope to learn whether similar mechanisms are at play as people’s brains undergo the metamorphosis that occurs during puberty.”
Parkinson’s Disease Brain Rhythms Detected
A team of scientists and clinicians at UC San Francisco has discovered how to detect abnormal brain rhythms associated with Parkinson’s by implanting electrodes within the brains of people with the disease.
The work may lead to developing the next generation of brain stimulation devices to alleviate symptoms for people with the disease.
Described this week in the journal Proceedings of the National Academy of Sciences (PNAS), the work sheds light on how Parkinson’s disease affects the brain, and is the first time anyone has been able to measure a quantitative signal from the disease within the cerebral cortex – the outermost layers of the brain that helps govern memory, physical movement and consciousness.
“Normally the individual cells of the brain are functioning independently much of the time, working together only for specific tasks,” said neurosurgeon Philip Starr, MD, PhD, a professor of neurological surgery at UCSF and senior author of the paper. But in Parkinson’s disease, he said, many brain cells display “excessive synchronization,” firing together inappropriately most of the time.
“They are locked into playing the same note as everyone else without exploring their own music,” Starr explained. This excessive synchronization leads to movement problems and other symptoms characteristic of the disease.
The new work also shows how deep brain stimulation (DBS), which electrifies regions deeper in the brain, below the cortex, can affect the cortex, itself. This discovery may change how DBS is used to treat Parkinson’s and other neurologically based movement disorders, and it may help refine the technique for other types of treatment.
Mouse brain cells live long and prosper
Mouse brain cells scamper close to eternal life: They can actually outlive their bodies. Mouse neurons transplanted into rat brains lived as long as the rats did, surviving twice as long as the mouse’s average life span, researchers report online February 25 in the Proceedings of the National Academy of Sciences.
The findings suggest that long lives might not mean deteriorating brains. “This could absolutely be true in other mammals — humans too,” says study author Lorenzo Magrassi, a neurosurgeon at the University of Pavia in Italy.
The findings are “very promising,” says Carmela Abraham, a neuroscientist at Boston University. “The question is: Can neurons live longer if we prolong our life span?” Magrassi’s experiment, she says, suggests the answer is yes.
One theory about aging, Magrassi says, is that every species has a genetically determined life span and that all the cells in the body wear out and die at roughly the same time. For the neurons his team studied, he says, “We have shown that this simple idea is certainly not true.”
Magrassi’s team surgically transplanted neurons from embryonic mice with an average life span of 18 months into rats. To do so, the researchers slipped a glass microneedle through the abdomens of anesthetized pregnant mice. Then, using a dissecting microscope and a tool to illuminate the corn-kernel-sized mouse embryos, the researchers scraped out tiny bits of brain tissue and injected the neurons into fetal rat brains. After the rat pups were born, Magrassi and colleagues waited as long as three years, until the animals were near death, to euthanize the rats and dissect their brains.
The transplanted mouse cells had linked up with the rat brain cells and developed into mature, working neurons, though they did retain their characteristic small size. Also, because Magrassi’s team had tagged the mouse cells to glow green, the researchers could distinguish between mouse and rat neurons. The mouse cells lived twice as long as they would have in a mouse brain, and they showed signs of aging similar to those of neighboring rat neurons.
Figuring out what’s helping the neurons survive could lead researchers to treatments for human neurodegenerative diseases, such as Parkinson’s and Alzheimer’s, Magrassi says.
A three molecule complex may be a target for treating Huntington’s disease, a genetic disorder affecting the brain. This finding by an international research team including scientists from the German Center for Neurodegenerative Diseases (DZNE) in Bonn and the University of Mainz was published in the online journal “Nature Communications”. The report states that the so-called MID1 complex controls the production of a protein which damages nerve cells.
The long DNA sequences in Huntington’s disease lead to changes in a certain protein called “Huntingtin”. The DNA is like an archive of blueprints for proteins. Errors in the DNA therefore result in defective proteins. “Huntingtin is essential for the organism’s survival. It is a multi-talent which is important for many processes,” emphasises Krauss. “If the protein is defective, brain cells may die.“
In the spotlight: protein synthesis
In the current study, the scientists around Sybille Krauss and the Mainz-based human geneticist Susann Schweiger took a closer look at a critical stage of protein production – translation. At this step, a copy of the DNA, the so-called messenger RNA, is processed by the cell’s protein factories. In patients with Huntington’s disease, the messenger RNA contains an unusually high number of consecutive CAG sequences – CAG representing the building plan for the amino acid glutamine.
These repetitive sequences have a direct consequence: more glutamine than normal is built into Huntingtin, which is therefore defective. Sybille Krauss and her colleagues have now identified a group of three molecules, which regulate the production of this protein. “We were able to show that this complex binds to the messenger RNA and controls the synthesis of defective Huntingtin,” says Krauss. When the scientists reduced the concentration of this so-called MID1 complex in the cell, production of the defective protein declined.
“If we could find a way of influencing this complex, for example with pharmaceuticals, it is quite possible that we could directly affect the production of defective Huntingtin. This kind of treatment would not just treat the symptoms but also the causes of Huntington’s disease,” says Krauss.
Background:Three molecules come together
The complex consists of MID1, from which it gets its name, and the proteins PP2Ac and S6K. “Every single one of these proteins is known to be important for translation. We have discovered that in the specific case of Huntington’s disease, they together bind to the CAG sequences. This was previously unknown. We also found that binding increases with repeat lengths,” says Krauss. “In sequences of normal length, we found only weak binding or none at all.”
The Bonn-based molecular biologist and her colleagues investigated the effect of the MID1 complex and the interaction between its components in a series of elaborate laboratory experiments. “This project took several years of research work,” says Krauss. Along with biochemical procedures, the scientists used cell cultures and analysed proteins from the brains of mice. The mice’s genetic code had been modified in such a way that it contained elongated CAG-repeats as it is typical for Huntington’s disease.
From previous studies it was already known that the protein MID1 tends to bind messenger RNAs. The scientists were now able to show that MID1 also attaches to messenger RNAs with excessively long CAG sequences. Furthermore, experiments showed that PP2Ac and S6K also bound the RNA in the presence of MID1. However, if the MID1 was depleted, this binding did not occur. “From this, we can conclude that these three proteins form a molecular complex, which binds to the RNA. MID1 is a key component. It actually seems to keep together its binding partners,” Krauss comments on the results of the experiments.
Complex controls protein production
The researchers were also able to prove that the MID1 complex controls the translation of RNA with excessively long CAG sequences. For this, they investigated various cell cultures. The cells produced either normal Huntingtin or – due to excessively long sequences in their DNA – a defective version of this protein. The scientists reduced the occurrence of MID1 inside the cells using a procedure known as “knock-down”. The elimination of this protein, which is a major part of the MID1 complex, had direct consequences: the production of defective Huntingtin declined. “However, it did not affect the production of normal Huntingtin,” emphazises Krauss. “This further proves that the MID1 complex specifically targets RNAs with excessively long CAG sequences.”
Highly specific
The Bonn-based molecular biologist sees this specific influence as a chance to treat Huntington’s disease: “The MID1 complex is a promising target for therapy. It indicates a possibility to suppress the production of defective Huntingtin only, while not affecting the production of normal Huntingtin. This is of particular significance, because the normal protein is also being produced in the patients’ bodies and it is important for the organism.”
A suitable active substance has yet to be found, says Krauss. However, the next developments are in sight: “We now want to test potential substances in the laboratory,” she says.
Ability of brain to protect itself from damage revealed
(Image: Matthias Kulka / Corbis)
The origin of an innate ability the brain has to protect itself from damage that occurs in stroke has been explained for the first time.
The Oxford University researchers hope that harnessing this inbuilt biological mechanism, identified in rats, could help in treating stroke and preventing other neurodegenerative diseases in the future.
'We have shown for the first time that the brain has mechanisms that it can use to protect itself and keep brain cells alive,' says Professor Alastair Buchan, Head of the Medical Sciences Division and Dean of the Medical School at Oxford University, who led the work.
The researchers report their findings in the journal Nature Medicine and were funded by the UK Medical Research Council and National Institute for Health Research.
Stroke is the third most common cause of death in the UK. Every year around 150,000 people in the UK have a stroke.
It occurs when the blood supply to part of the brain is cut off. When this happens, brain cells are deprived of the oxygen and nutrients they need to function properly, and they begin to die.
'Time is brain, and the clock has started immediately after the onset of a stroke. Cells will start to die somewhere from minutes to at most 1 or 2 hours after the stroke,' says Professor Buchan.
This explains why treatment for stroke is so dependent on speed. The faster someone can reach hospital, be scanned and have drugs administered to dissolve any blood clot and get the blood flow re-started, the less damage to brain cells there will be.
It has also motivated a so-far unsuccessful search for ‘neuroprotectants’: drugs that can buy time and help the brain cells, or neurons, cope with damage and recover afterwards.
The Oxford University research group have now identified the first example of the brain having its own built-in form of neuroprotection, so-called ‘endogenous neuroprotection’.
They did this by going back to an observation first made over 85 years ago. It has been known since 1926 that neurons in one area of the hippocampus, the part of the brain that controls memory, are able to survive being starved of oxygen, while others in a different area of the hippocampus die. But what protected that one set of cells from damage had remained a puzzle until now.
'Previous studies have focused on understanding how cells die after being depleted of oxygen and glucose. We considered a more direct approach by investigating the endogenous mechanisms that have evolved to make these cells in the hippocampus resistant,' explains first author Dr Michalis Papadakis, Scientific Director of the Laboratory of Cerebral Ischaemia at Oxford University.
Working in rats, the researchers found that production of a specific protein called hamartin allowed the cells to survive being starved of oxygen and glucose, as would happen after a stroke.
They showed that the neurons die in the other part of the hippocampus because of a lack of the hamartin response.
The team was then able to show that stimulating production of hamartin offered greater protection for the neurons.
Professor Buchan says: ‘This is causally related to cell survival. If we block hamartin, the neurons die when blood flow is stopped. If we put hamartin back, the cells survive once more.’
Finally, the researchers were able to identify the biological pathway through which hamartin acts to enable the nerve cells to cope with damage when starved of energy and oxygen.
The group points out that knowing the natural biological mechanism that leads to neuroprotection opens up the possibility of developing drugs that mimic hamartin’s effect.
Professor Buchan says: ‘There is a great deal of work ahead if this is to be translated into the clinic, but we now have a neuroprotective strategy for the first time. Our next steps will be to see if we can find small molecule drug candidates that mimic what hamartin does and keep brain cells alive.
'While we are focussing on stroke, neuroprotective drugs may also be of interest in other conditions that see early death of brain cells including Alzheimer's and motor neurone disease,' he suggests.
(Source: eurekalert.org)
Concepts in our minds – from Luke Skywalker to our grandmother - are represented by their own distinct group of neurons, according to new research involving a University of Leicester neuroscientist.
The research, by neuroscientist Professor Rodrigo Quian Quiroga from the University of Leicester Centre for Systems Neuroscience together with Professor Itzhak Fried, of the UCLA David Geffen School of Medicine, Tel Aviv Sourasky Medical Center and Tel Aviv University, and Professor Christof Koch, of the California Institute of Technology and Allen Institute for Brain Science, Seattle, is featured in a recent article of the prestigious Scientific American magazine.
Recent experiments during brain surgeries have shown that small groups of brain cells are responsible for encoding memories of specific people or objects.
These neurons may also represent different variations of one thing – from the name of a person to their appearance from many different viewpoints.
The researchers believe that single concepts may be held in as little as thousands of neurons or less – a tiny fraction of the billion or so neurons contained in the medial temporal lobe, which is a memory related structure within the brain.
The group were able to monitor the brain activity of consenting patients undergoing surgery to treat epilepsy. This allowed the team to monitor the activity of single neurons in conscious patients while they looked at images on laptop screens, creating and recalling memories.
In previous experiments, they had found that single neurons would ‘fire’ for specific concepts – such as Luke Skywalker – even when they were viewing images of him from different angles or simply hearing or reading his name.
They have also found that single neurons can also fire to related people and objects – for instance, the neuron that responded to Luke Skywalker also fired to Yoda, another Jedi from Star Wars.
They argue that relatively small groups of neurons hold concepts like Luke Skywalker and that related concepts such as Yoda are held by some but not all of the same neurons. At the same time, a completely separate set of neurons would hold an unrelated concept like Jennifer Aniston.
The group believes this partially overlapping representation of related concepts are the neural underpinnings of encoding associations, a key memory function.
Professor Quian Quiroga said: “After the first thrill when finding neurons in the human hippocampus with such remarkable firing characteristics, converging evidence from experiments we have been carrying out in the last years suggests that we may be hitting one of the key mechanisms of memory formation and recall.
“The abstract representation of concepts provided by these neurons is indeed ideal for representing the meaning of the sensory stimuli around us, the internal representation we use to form and retrieve memories. These concepts cells, we believe, are the building blocks of memory functions.”
Cigarette smoke damages the lungs, but it also wreaks havoc in the brain, a study in mice suggests. Signs of Alzheimer’s disease increased in the brains of animals that breathed cigarette smoke for four months, scientists report February 19 in Nature Communications.
The relationship between smoking and Alzheimer’s in people is murky. Some evidence from the 1990s suggested that smoking actually protected people against Alzheimer’s, presumably by stimulating nicotine-detecting brain cells. More recent studies have found that smoking ups the odds of the disease.
To see what cigarettes do to the brain, scientists led by Claudio Soto of the University of Texas Medical School at Houston turned to mice. In animals bred to show signs of Alzheimer’s, cigarette smoke (one cigarette’s worth in air the mouse breathed for an hour, five days a week) worsened aspects of the disease. Compared with mice that weren’t exposed, mice exposed to smoke had several signs of Alzheimer’s: they had more amyloid beta plaques, a higher load of abnormal tau protein and more severe inflammation in their brains.
The scientists don’t know yet how cigarette smoke causes these changes, or whether a similar process happens in people.
Cooling may prevent trauma-induced epilepsy
In the weeks, months and years after a severe head injury, patients often experience epileptic seizures that are difficult to control. A new study in rats suggests that gently cooling the brain after injury may prevent these seizures.
“Traumatic head injury is the leading cause of acquired epilepsy in young adults, and in many cases the seizures can’t be controlled with medication,” says senior author Matthew Smyth, MD, associate professor of neurological surgery and of pediatrics at Washington University School of Medicine in St. Louis. “If we can confirm cooling’s effectiveness in human trials, this approach may give us a safe and relatively simple way to prevent epilepsy in these patients.”
The researchers reported their findings in Annals of Neurology.
Cooling the brain to protect it from injury is not a new concept. Cooling slows down the metabolic activity of nerve cells, and scientists think this may make it easier for brain cells to survive the stresses of an injury.
Doctors currently cool infants whose brains may have had inadequate access to blood or oxygen during birth. They also cool some heart attack patients to reduce peripheral brain damage when the heart stops beating.
Smyth has been exploring the possibility of using cooling to prevent seizures or reduce their severity.
“Warmer brain cells seem to be more electrically active, and that may increase the likelihood of abnormal electrical discharges that can coalesce to form a seizure,” Smyth says. “Cooling should have the opposite effect.”
Smyth and colleagues at the University of Washington and the University of Minnesota test potential therapies in a rat model of brain injury. These rats develop chronic seizures weeks after the injury.
Researchers devised a headset that cools the rat brain. They were originally testing its ability to stop seizures when they noticed that cooling seemed to be not only stopping but also preventing seizures.
Scientists redesigned the study to focus on prevention. Under the new protocols, they put headsets on some of the rats that cooled their brains by less than 4 degrees Fahrenheit. Another group of rats wore headsets that did nothing. Scientists who were unaware of which rats they were observing monitored them for seizures during treatment and after the headsets were removed.
Rats that wore the inactive headset had progressively longer and more severe seizures weeks after the injury, but rats whose brains had been cooled only experienced a few very brief seizures as long as four months after injury.
Brain injury also tends to reduce cell activity at the site of the trauma, but the cooling headsets restored the normal activity levels of these cells.
The study is the first to reduce injury-related seizures without drugs, according to Smyth, who is director of the Pediatric Epilepsy Surgery program at St. Louis Children’s Hospital.
“Our results show that the brain changes that cause this type of epilepsy happen in the days and weeks after injury, not at the moment of injury or when the symptoms of epilepsy begin,” says Smyth. “If clinical trials confirm that cooling has similar effects in humans, it could change the way we treat patients with head injuries, and for the first time reduce the chance of developing epilepsy after brain injury.”
Smyth and his colleagues have been testing cooling devices in humans in the operating room, and are planning a multi-institutional trial of an implanted focal brain cooling device to evaluate the efficacy of cooling on established seizures.
Omega-3 Lipid Emulsions Markedly Protect Brain After Stroke in Mouse Study
Triglyceride lipid emulsions rich in an omega-3 fatty acid injected within a few hours of an ischemic stroke can decrease the amount of damaged brain tissue by 50 percent or more in mice, reports a new study by researchers at Columbia University Medical Center.
The results suggest that the emulsions may be able to reduce some of the long-term neurological and behavioral problems seen in human survivors of neonatal stroke and possibly of adult stroke, as well. The findings were published today in the journal PLoS One.
Currently, clot-busting tPA (recombinant tissue-type plasminogen activator) is the only treatment shown to improve recovery from ischemic stroke. If administered soon after stroke onset, the drug can restore blood flow to the brain but may not prevent injured, but potentially salvageable, neurons from dying.
Drugs with neuroprotective qualities that can prevent the death of brain cells damaged by stroke are needed, but even after 30 years of research and more than 1000 agents tested in animals, no neuroprotectant has been found effective in people.
Omega-3 fatty acids may have more potential as neuroprotectants because they affect multiple biochemical processes in the brain that are disturbed by stroke, said the study’s senior author, Richard Deckelbaum, MD, director of the Institute of Human Nutrition at Columbia’s College of Physicians & Surgeons. “The findings also may be applicable to other causes of ischemic brain injury in newborns and adults,” added co-investigator Vadim S. Ten, MD, PhD, an associate professor of pediatrics from the Department of Pediatrics at Columbia.
The effects of the omega-3 fatty acids include increasing the production of natural neuroprotectants in the brain, reducing inflammation and cell death, and activating genes that may protect brain cells. Omega-3 fatty acids also markedly reduce the release of harmful oxidants into the brain after stroke. “In most clinical trials in the past, the compounds tested affected only one pathway. Omega-3 fatty acids, in contrast, are very bioactive molecules that target multiple mechanisms involved in brain death after stroke,” Dr. Deckelbaum said.
The study revealed that an emulsion containing only DHA (docosahexaenoic acid), but not EPA (eicosapentaenoic acid), in a triglyceride molecule reduced the area of dead brain tissue by about 50 percent or more even when administered up to two hours after the stroke. Dr. Deckelbaum noted, “Since mice have a much faster metabolism than humans, longer windows of time for therapeutic effect after stroke are likely in humans.” Eight weeks after the stroke, much of the “saved” mouse brain tissue was still healthy, and no toxic effects were detected.
(Image: Shutterstock)
Neuroscientist Sheds Light on Cause for ‘Chemo Brain’
Study finds fog-like condition related to chemotherapy’s effect on new brain cells and rhythms.
It’s not unusual for cancer patients being treated with chemotherapy to complain about not being able to think clearly, connect thoughts or concentrate on daily tasks. The complaint – often referred to as chemo-brain – is common. The scientific cause, however, has been difficult to pinpoint.
New research by Rutgers University behavioral neuroscientist Tracey Shors offers new clues for this fog-like condition, medically known as chemotherapy-induced cognitive impairment. In a featured article published in the European Journal of Neuroscience, Shors and her colleagues argue that prolonged chemotherapy decreases the development of new brain cells, a process known as neurogenesis, and disrupts ongoing brain rhythms in the part of the brain responsible for making new memories. Both, she says, are affected by learning and in some cases are necessary for learning to occur.
“One of the things that these brain rhythms do is to connect information across brain regions,” says Shors, Professor II in the Department of Psychology and Center for Collaborative Neuroscience at Rutgers. “We are starting to have a better understanding of how these natural rhythms are used in the process of communication and how they change with experience.”
Working in the Shors laboratory, postdoctoral fellow Miriam S. Nokia from the Department of Psychology at the University of Jyvaskyla in Finland and Rutgers neuroscience graduate student Megan Anderson treated rats with a chemotherapy drug – temozolomide (TMZ) – used on individuals with either malignant brain tumors or skin cancer to stop rapidly dividing cells that have gone out of control and resulted in cancer.
In this study, scientists found that the production of new healthy brain cells treated with the TMZ was reduced in the hippocampus by 34 percent after being caught in the crossfire of the drug’s potency. The cell loss, coupled with the interference in brain rhythms, resulted in the animal being unable to learn difficult tasks.
Shors says the rats had great difficulty learning to associate stimulus events if there was a time gap between the activities but could learn simple task if the stimuli were not separated in time. Interestingly, she says, the drug did not disrupt the memories that were already present when the treatment began.
For cancer patients undergoing long-term chemotherapy this could mean that although they are able to do simple everyday tasks, they find it difficult to do more complicated activities like processing long strings of numbers, remembering recent conversations, following instructions and setting priorities. Studies indicate that while most cancer patients experience short-term memory loss and disordered thinking, about 15 percent of cancer patients suffer more long-lasting cognitive problems as a result of the chemotherapy treatment.
“Chemotherapy is an especially difficult time as patients are learning how to manage their treatment options while still engaging in and appreciating life. The disruptions in brain rhythms and neurogenesis during treatment may explain some of the cognitive problems that can occur during this time. The good news is that these effects are probably not long-lasting,” says Shors.
(Source: news.rutgers.edu)