Posts tagged science
Articles and news from the latest research reports.
Existence of new neuron repair pathway discovered
Most of your neurons can’t be replaced.
Other parts of your body – such as skin and bone – can be replaced by the body growing new cells, but when you injure your neurons, you can’t just grow new ones; instead, the existing cells have to repair themselves.
In the case of axon injury, the neuron is able to repair or sometimes even fully regenerate its axon. But neurons have two sides – the axon (which sends signals to other cells) and the dendrite (which receives signals from other cells).
Melissa Rolls, an associate professor of biochemistry and molecular biology at Penn State and director of the Huck Institutes’ Center for Cellular Dynamics, has done extensive comparisons of axons and dendrites – culminating recently in a paper published in Cell Reports.
“We know that the axon side can repair itself,” says Rolls, “and we know a bunch of the molecular players. But we really didn’t know whether neurons have the same capacity to regenerate their dendrites, and so that’s what we set out to find in this study.”
“Our lab uses a Drosophila model system, where the dendrites are very accessible to manipulation,” she says, “so we decided that we would start by removing all the dendrites from the neurons to see if they could regenerate. We didn’t start with anything subtle, like taking off just a few dendrites. We said ‘Let’s just push the system to its maximum and see if this is even possible.’ And we were surprised because we found that not only is it possible, it’s actually much faster than axon regeneration: at least in the cells that we’re using, axon regeneration takes a day or two to initiate, while dendrite regeneration typically initiates within four to six hours and it works really well. All the cells where we removed the dendrites grew new dendrites – none of them died; so it’s clear that these cells have a way to both detect dendrite injury and initiate regrowth of the injured part.”
(Image caption: During the learning processes, extensions grow on neurons. Synapses are located at the end of these extensions (left: as seen in nature; right: reconstruction). When the synapse growth is based on the correlated development of all synaptic components, it can remain stable for long periods of time. Credit: © MPI of Neurobiology/ Meyer)
Synapses – stability in transformation
Nothing lasts forever. This principle also applies to the proteins that make up the points of contact between our neurons. It is due to these proteins that the information arriving at a synapse can be transmitted and then received by the next neuron. When we learn something, new synapses are created or existing ones are strengthened. To enable us to retain long-term memories, synapses must remain stable for long periods of time, up to an entire lifetime. Researchers at the Max Planck Institute of Neurobiology in Martinsried near Munich have found an explanation as to how a synapse achieves remaining stable for a long time despite the fact that its proteins must be renewed regularly.
Learning in the laboratory
“We were interested first of all in what happens to the different components of a synapse when it grows during a learning process,” explains study leader Volker Scheuss. An understanding of how the components grow could also provide information about the long-term stability of synapses. Hence, the researchers studied the growth of synapses in tissue culture dishes following exposure to a (learning) stimulus. To do this, they deliberately activated individual synapses using the neurotransmitter glutamate: scientists have long known that glutamate plays an important role in learning processes and stimulates the growth of synapses. Over the following hours, the researchers observed the stimulated synapses and control synapses under a 2-photon microscope. To confirm the observed effects, they then examined individual synapses with the help of an electron microscope. “When you consider that individual synapses are only around one thousandth of a millimetre in size, this was quite a Sisyphean task,” says Tobias Bonhoeffer, the Director of the department where the research was carried out.
Synaptic stability – a concerted effort
The scientists discovered that during synapse growth the different protein structures always grew coordinated with each other. If one structural component was enlarged alone, or in a way that was not correctly correlated with the other components, its structural change would collapse soon after. Synapses with such incomplete changes cannot store any long-term memories.
The study findings show that the order and interaction between synaptic components is finely tuned and correlated. “In a system of this kind, it should be entirely possible to replace individual proteins while the rest of the structure maintains its integrity,” says Scheuss. However, if an entire group of components breaks away, the synapse is destabilised. This is also an important process given that the brain could not function correctly without the capacity to forget things. Hence, the study’s results provide not only important insight into the functioning and structure of synapses, they also establish a basis for a better understanding of memory loss, for example in the case of degenerative brain diseases.
Why your nose can be a pathfinder
When I was a child I used to sit in my grandfather’s workshop, playing with wood shavings. Freshly shaven wood has a distinct smell of childhood happiness, and whenever I get a whiff of that scent my brain immediately conjures up images of my grandfather at his working bench, the heat from the fireplace and the dog next to it.
Researchers at the Kavli Institute for Systems Neuroscience have recently discovered the process behind this phenomenon. The brain, it turns out, connects smells to memories through an associative process where neural networks are linked through synchronised brain waves of 20-40 Hz.
– We all know that smell is connected to memories, Kei Igarashi, lead author, explains.– We know that neurons in different brain regions need to oscillate in synchrony for these regions to speak effectively to each other. Still, the relationship between interregional coupling and formation of memory traces has remained poorly understood. So we designed a task to investigate how odour-place representation evolved in the entorhinal and hippocampal region, to figure out whether learning depends on coupling of oscillatory networks.
Smell guides the way in maze
The researchers designed a maze for rats, where a rat would see a hole to poke its nose into. When poking into the hole, the rat was presented with one of two alternative smells. One smell told the rat that food would be found in the left food cup behind the rat. The other smell told it that there was food in the right cup. The rat would soon learn which smell would lead to a reward where. After three weeks of training, the rats chose correctly on more than 85% of the trials. In order to see what happened inside the brain during acquisition, 16–20 electrode pairs were inserted in the hippocampus and in different areas of the entorhinal cortex.
After the associations between smell and place were well established, the researchers could see a pattern of brain wave activity (the electrical signal from a large number of neurons) during retrieval.
Coherent brain activity evolves with learning
– Immediately after the rat is exposed to the smell there is a burst in activity of 20–40 Hz waves in a specific connection between an area in the entorhinal cortex, lateral entorhinal cortex (LEC), and an area in the hippocampus, distal CA1 (dCA1), while a similar strong response was not observed in other connections, Igarashi explains.
This coherence of 20–40 Hz activity in the LEC and dCA1 evolved in parallel with learning, with little coherence between these areas before training started. By the time the learning period was over, cells were phase locked to the oscillation and a large portion of the cells responded specifically to one or the other of the smell-odour pairs.
Long distance communication in brain mediated by waves
– This is not the first time we observe that the brain uses synchronised wave activity to establish network connections, Edvard Moser, director of the Kavli Institute for Systems Neuroscience says. – Both during encoding and retrieval of declarative memories there is an interaction between these areas mediated through gamma and theta oscillations. However, this is the first study to relate the development of a specific band of oscillations to memory performance in the hippocampus. Together, the evidence is now piling up and pointing in the direction of cortical oscillations as a general mechanism for mediating interactions among functionally specialised neurons in distributed brain circuits.
So, there you have it – the signals from your nose translate and connect to memories in an orchestrated symphony of signals in your head. Each of these memories connects to a location, pinpointed on your inner map. So when you feel a wave of reminiscence triggered by a fragrance, think about how waves created this connection in the first place.
Genetic Pre-Disposition Toward Exercise and Mental Development May be Linked
University of Missouri researchers have previously shown that a genetic pre-disposition to be more or less motivated to exercise exists. In a new study, Frank Booth, a professor in the MU College of Veterinary Medicine, has found a potential link between the genetic pre-disposition for high levels of exercise motivation and the speed at which mental maturation occurs.
For his study, Booth selectively bred rats that exhibited traits of either extreme activity or extreme laziness. Booth then put the rats in cages with running wheels and measured how much each rat willingly ran on their wheels during a six-day period. He then bred the top 26 runners with each other and bred the 26 rats that ran the least with each other. They repeated this process through 10 generations and found that the line of running rats chose to run 10 times more than the line of “lazy” rats.
Booth studied the brains of the rats and found much higher levels of neural maturation in the brains of the active rats than in the brains of the lazy rats.
“We looked at the part of the brain known as the ‘grand central station,’ or the hub where the brain is constantly sending and receiving signals,” Booth said. “We found a big difference between the amount of molecules present in the brains of active rats compared to the brains of lazy rats. This suggests that the active rats were experiencing faster development of neural pathways than the lazy rats.”
Booth says these findings may suggest a link between the genes responsible for exercise motivation and the genes responsible for mental development. He also says this research hints that exercising at a young age could help develop more neural pathways for motivation to be physically active.
“This study illustrates a potentially important link between exercise and the development of these neural pathways,” Booth said. “Ultimately, this could show the benefits of exercise for mental development in humans, especially young children with constantly growing brains.”
(Source: munews.missouri.edu)
Chrono, the last piece of the circadian clock puzzle?
In an article published today in PLOS Biology, researchers from the RIKEN Brain Science Institute in Japan report the identification of Chrono, a gene involved in the regulation of the body clock in mammals and that might be a key component of the body’s response to stress.
All organisms, from mammals to fungi, have daily cycles controlled by a tightly regulated internal clock, called the circadian clock. The whole-body circadian clock, influenced by the exposure to light, dictates the wake-sleep cycle. At the cellular level, the clock is controlled by a complex network of genes and proteins that switch each other on and off based on cues from their environment.
Most genes involved in the regulation of the circadian clock have been characterized, but Akihiro Goriki, Toru Takumi and their colleagues from RIKEN and Hiroshima University in Japan and University of Michigan in the United States knew that a key component was missing and sough to uncover it in mammals.
In the study, the team performed a genome-wide chromatin immunoprecipitation analysis for genes that were the target of BMAL1, a core clock component that binds to many other clock genes, regulating their transcription.
The authors characterize a new circadian gene that they name Chrono. They show that CHRONO functions as a transcriptional repressor of the negative feedback loop in the mammalian clock: the protein CHRONO binds to the regulatory region of clock genes, with its repressor function oscillating in a circadian manner. The expression of core clock genes is altered in mice lacking the Chrono gene, and the mice have longer circadian cycles.
"These results suggest that Chrono functions as a core clock repressor,” conclude the authors.
In addition, they demonstrate that the repression mechanism of Chrono is under epigenetic control and links, via a glucocorticoid receptor, to metabolic pathways triggered by behavioral stress.
These findings are confirmed by another study by the University of Pennsylvania, also published in PLOS Biology today. In the study, John Hogenesch and his team prove the existence of Chrono using a computer-based analysis.
Scientists explain how memories stick together
Scientists at the Salk Institute have created a new model of memory that explains how neurons retain select memories a few hours after an event.
This new framework provides a more complete picture of how memory works, which can inform research into disorders liked Parkinson’s, Alzheimer’s, post-traumatic stress and learning disabilities.
"Previous models of memory were based on fast activity patterns," says Terrence Sejnowski, holder of Salk’s Francis Crick Chair and a Howard Hughes Medical Institute Investigator. "Our new model of memory makes it possible to integrate experiences over hours rather than moments."
Over the past few decades, neuroscientists have revealed much about how long-term memories are stored. For significant events—for example, being bit by a dog—a number of proteins are quickly made in activated brain cells to create the new memories. Some of these proteins linger for a few hours at specific places on specific neurons before breaking down.
This series of biochemical events allow us to remember important details about that event—such as, in the case of the dog bite, which dog, where it was located and so on.
One problem scientists have had with modeling memory storage is explaining why only selective details and not everything in that 1-2 hour window is strongly remembered. By incorporating data from previous literature, Sejnowski and first author Cian O’Donnell, a Salk postdoctoral researcher, developed a model that bridges findings from both molecular and systems observations of memory to explain how this 1-2 hour memory window works. The work is detailed in the latest issue of Neuron.
Using computational modeling, O’Donnell and Sejnowski show that, despite the proteins being available to a number of neurons in a given circuit, memories are retained when subsequent events activate the same neurons as the original event. The scientists found that the spatial positioning of proteins at both specific neurons and at specific areas around these neurons predicts which memories are recorded. This spatial patterning framework successfully predicts memory retention as a mathematical function of time and location overlap.
"One thing this study does is link what’s happing in memory formation at the cellular level to the systems level," says O’Donnell. "That the time window is important was already established; we worked out how the content could also determine whether memories were remembered or not. We prove that a set of ideas are consistent and sufficient to explain something in the real world."
The new model also provides a potential framework for understanding how generalizations from memories are processed during dreams.
While much is still unknown about sleep, research suggests that important memories from the day are often cycled through the brain, shuttled from temporary storage in the hippocampus to more long-term storage in the cortex. Researchers observed most of this memory formation in non-dreaming sleep. Little is known about if and how memory packaging or consolidation is done during dreams. However, O’Donnell and Sejnowski’s model suggests that some memory retention does happen during dreams.
"During sleep there’s a reorganizing of memory—you strengthen some memories and lose ones you don’t need anymore," says O’Donnell. "In addition, people learn abstractions as they sleep, but there was no idea how generalization processes happen at a neural level."
By applying their theoretical findings on overlap activity within the 1-2 hour window, they came up with a theoretical model for how the memory abstraction process might work during sleep.
(Source: salk.edu)
Cancer drugs block dementia-linked brain inflammation
A class of drugs developed to treat immune-related conditions and cancer – including one currently in clinical trials for glioblastoma and other tumors – eliminates neural inflammation associated with dementia-linked diseases and brain injuries, according to UC Irvine researchers.
In their study, assistant professor of neurobiology & behavior Kim Green and colleagues discovered that the drugs, which can be delivered orally, eradicated microglia, the primary immune cells of the brain. These cells exacerbate many neural diseases, including Alzheimer’s and Parkinson’s, as well as brain injury.
“Because microglia are implicated in most brain disorders, we feel we’ve found a novel and broadly applicable therapeutic approach,” Green said. “This study presents a new way to not just modulate inflammation in the brain but eliminate it completely, making this a breakthrough option for a range of neuroinflammatory diseases.”
The researchers focused on the impact of a class of drugs called CSF1R inhibitors on microglial function. In mouse models, they learned that inhibition led to the removal of virtually all microglia from the adult central nervous system with no ill effects or deficits in behavior or cognition. Because these cells contribute to most brain diseases – and can harm or kill neurons – the ability to eradicate them is a powerful advance in the treatment of neuroinflammation-linked disorders.
Green said his group tested several selective CSF1R inhibitors that are under investigation as cancer treatments and immune system modulators. Of these compounds, they found the most effective to be a drug called PLX3397, created by Plexxikon Inc., a Berkeley, Calif.-based biotechnology company and member of the Daiichi Sankyo Group. PLX3397 is currently being evaluated in phase one and two clinical trials for multiple cancers, including glioblastoma, melanoma, breast cancer and leukemia.
Crucially, microglial elimination lasted only as long as treatment continued. Withdrawal of inhibitors produced a rapid repopulation of cells that then grew into new microglia, said Green, who’s a member of UC Irvine’s Institute for Memory Impairments and Neurological Disorders.
This means that eradication of these immune cells is fully reversible, allowing researchers to bring microglia back when desired. Green added that this work is the first to describe a new progenitor/potential stem cell in the central nervous system outside of neurogenesis, a discovery that points to novel opportunities for manipulating microglial populations during disease.
(Source: news.uci.edu)
Gene variant puts women at higher risk of Alzheimer’s than it does men
Carrying a copy of a gene variant called ApoE4 confers a substantially greater risk for Alzheimer’s disease on women than it does on men, according to a new study by researchers at the Stanford University School of Medicine.
The scientists arrived at their findings by analyzing data on large numbers of older individuals who were tracked over time and noting whether they had progressed from good health to mild cognitive impairment — from which most move on to develop Alzheimer’s disease within a few years — or to Alzheimer’s disease itself.
The discovery holds implications for genetic counselors, clinicians and individual patients, as well as for clinical-trial designers. It could also help shed light on the underlying causes of Alzheimer’s disease, a progressive neurological syndrome that robs its victims of their memory and ability to reason. Its incidence increases exponentially after age 65. An estimated one in every eight people past that age in the United States has Alzheimer’s. Experts project that by mid-century, the number of Americans with Alzheimer’s will more than double from the current estimate of 5-6 million.
According to the Alzheimer’s Association, it is already the nation’s most expensive disease, costing more than $200 million annually. (The epidemiology of mild cognitive impairment is fuzzier, but this gateway syndrome is clearly more widespread than Alzheimer’s.)
New insight into SIDS deaths points to lack of oxygen
Research at the University of Adelaide has shed new light onto the possible causes of sudden infant death syndrome (SIDS), which could help to prevent future loss of children’s lives.
In a world-first study, researchers in the University’s School of Medical Sciences have found that telltale signs in the brains of babies that have died of SIDS are remarkably similar to those of children who died of accidental asphyxiation.
"This is a very important result. It helps to show that asphyxia rather than infection or trauma is more likely to be involved in SIDS deaths," says the leader of the project, Professor Roger Byard AO, Marks Professor of Pathology at the University of Adelaide and Senior Specialist Forensic Pathologist with Forensic Science SA.
The study compared 176 children who died from head trauma, infection, drowning, asphyxia and SIDS.
Researchers were looking at the presence and distribution of a protein called β-amyloid precursor protein (APP) in the brain. This “APP staining”, as it’s known, could be an important tool for showing how children have died. This is the first time a detailed study of APP has been undertaken in SIDS cases.
"All 48 of the SIDS deaths we looked at showed APP staining in the brain," Professor Byard says.
"The staining by itself does not necessarily tell us the cause of death, but it can help to clarify the mechanism.
"The really interesting point is that the pattern of APP staining in SIDS cases - both the amount and distribution of the staining - was very similar to those in children who had died from asphyxia."
Professor Byard says that in one case, the presence of APP staining in a baby who had died of SIDS led to the identification of a significant sleep breathing problem, or apnoea, in the deceased baby’s sibling.
"This raised the possibility of an inherited sleep apnoea problem, and this knowledge could be enough to help save a child’s life," Professor Byard says.
"Because of the remarkable similarity in SIDS and asphyxia cases, the question is now: is there an asphyxia-based mechanism of death in SIDS? We don’t know the answer to that yet, but it looks very promising."
This study was conducted at the University of Adelaide by visiting postdoctoral researcher Dr Lisbeth Jensen from Aarhus University Hospital, Denmark, and was funded by SIDS and Kids South Australia. The results have been published in the journal Neuropathology and Applied Neurobiology.
"This work also fits in very well with collaborative research that is currently being undertaken between the University of Adelaide and Harvard University, on chemical changes in parts of the brain that control breathing," Professor Byard says.
(Source: adelaide.edu.au)
Study Examines Vitamin D Deficiency and Cognition Relationship
Vitamin D deficiency and cognitive impairment are common in older adults, but there isn’t a lot of conclusive research into whether there’s a relationship between the two.
A new study from Wake Forest Baptist Medical Center published online ahead of print this month in the Journal of the American Geriatrics Society enhances the existing literature on the subject.
“This study provides increasing evidence that suggests there is an association between low vitamin D levels and cognitive decline over time,” said lead author Valerie Wilson, M.D., assistant professor of geriatrics at Wake Forest Baptist. “Although this study cannot establish a direct cause and effect relationship, it would have a huge public health implication if vitamin D supplementation could be shown to improve cognitive performance over time because deficiency is so common in the population.”
Wilson and colleagues were interested in the association between vitamin D levels and cognitive function over time in older adults. They used data from the Health, Aging and Body composition (Health ABC) study to look at the relationship. The researchers looked at 2,777 well-functioning adults aged 70 to 79 whose cognitive function was measured at the study’s onset and again four years later. Vitamin D levels were measured at the 12-month follow-up visit.
The Health ABC study cohort consists of 3,075 Medicare-eligible, white and black, well-functioning, community-dwelling older adults who were recruited between April 1997 and June 1998 from Pittsburgh, Pa., and Memphis, Tenn.
“With just the baseline observational data, you can’t conclude that low vitamin D causes cognitive decline. When we looked four years down the road, low vitamin D was associated with worse cognitive performance on one of the two cognitive tests used,” Wilson said. “It is interesting that there is this association and ultimately the next question is whether or not supplementing vitamin D would improve cognitive function over time.”
Wilson said randomized, controlled trials are needed to determine whether vitamin D supplementation can prevent cognitive decline and definitively establish a causal relationship.
“Doctors need this information to make well-supported recommendations to their patients,” Wilson said. “Further research is also needed to evaluate whether specific cognitive domains, such as memory versus concentration, are especially sensitive to low vitamin D levels.”