Posts tagged hippocampus
Articles and news from the latest research reports.
Hippocampal activity during music listening exposes the memory-boosting power of music
For the first time the hippocampus—a brain structure crucial for creating long-lasting memories—has been observed to be active in response to recurring musical phrases while listening to music. Thus, the hippocampal involvement in long-term memory may be less specific than previously thought, indicating that short and long-term memory processes may depend on each other after all.
The study was conducted at the University of Jyväskylä and the AMI Center of Aalto University, by a group of researchers led by Academy Professor Petri Toiviainen, the Finnish Centre for Interdisciplinary Music Research (CIMR) at the University of Jyväskylä, and Dr. Elvira Brattico, Aalto University and the University of Helsinki. Results of the study were published in Cortex, a journal devoted to the study of the nervous system and behaviour.
“Our study basically shows an increase of activity in the medial temporal lobe areas—best known for being essential for long term memory—when musical motifs in the piece were repeated. This means that the lobe areas are engaged in the short-term recognition of musical phrases,” explains Iballa Burunat, the leading author of the study. Dr. Brattico adds: “Importantly, this hadn’t been observed before in music neuroscience.”
A fundamental highlight of the study is the use of a setting that is more natural than those traditionally employed in neuroscience: the participants’ only task was to attentively listen to an Argentinian tango from beginning to end. This kind of music provides well-defined, salient musical motifs that are easy to follow. They can be used to study recognition processes in the brain without having to resort to sound created in a lab. By using this more realistic approach, the researchers were able to identify brain areas involved in motif tracking without having to rely on the participants’ ability to self-report, which would have constrained the study of brain processes.
“We think that our novel method allowed us to uncover this phenomenon. In other words, the identified areas may also be related to the formation of a more permanent memory trace of a musical piece, enabled precisely by the very use of a real-life stimulus (the recording of a live performance) in a realistic situation where participants just listen to the music as their brain responses are recorded,” Iballa Burunat goes on to explain. Listening to the music from beginning to end may have imprinted the participants with a long lasting memory of the tune. This might not be expected were the participants exposed to a simpler stimulus in controlled conditions, as is the case in most studies in music and memory.
Although a real-life setting may be sufficient to trigger the involvement of the hippocampus, another explanation could lie in music’s capacity to elicit emotions. “We cannot ignore music’s emotional power which is thought to be crucial for the mnemonic power of music as to how and what we remember. There is evidence on the robust integration of music, memory and emotion—take for instance autobiographical memories. So it wouldn’t be surprising that the emotional content of the music may well have been a factor in triggering these limbic responses,” she continues. This makes sense, since the chosen musical piece by Astor Piazzolla was a tribute to his father after his sudden death, and so the main purpose of the piece was to be of a deeply emotional nature”. Certainly, the hippocampus—as part of the limbic system—is connected to neural circuitry involved in emotional behavior, and ongoing research suggests that emotional events seem to be more memorable than neutral ones. The authors emphasize that these results should motivate similar approaches to study verbal or visual short term memory by tracking the themes or repetitive structures of a given stimulus. Moreover, the study has implications for neurodegenerative diseases associated with hippocampal atrophy, like Alzheimer’s. “Music may positively affect patients if used wisely to stimulate their hippocampi, and thus their memory system,” Academy Professor Petri Toiviainen indicates. A better understanding of the link between music and memory could have widespread repercussions, leading to novel interventions to rehabilitate or improve the life quality of patients with neurodegenerative conditions.
Clever Suppression in the Brain
The hippocampus is a small structure in the brains of mammals that plays a crucial role in processing input from our senses and allows perceptions to be stored as memories. Nerve cells that inhibit the activity of other cells have now been shown to play a much larger and more complex role in these processes than previously assumed. Teams led by Prof. Dr. Marlene Bartos from the Cluster of Excellence BrainLinks-BrainTools at the University of Freiburg and Prof. Dr. Imre Vida from the Cluster of Excellence NeuroCure at the hospital Charité in Berlin report these findings in the current issue of the Journal of Neuroscience.
(Image caption: Three different cell types in the hippocampus (BC, HCP, and HIPP) were previously known to have different morphologies (top). New research shows that they respond to electrical stimulation (black traces) by inhibiting other nerve cells in very different patterns (bottom), allowing for more powerful information processing. Credit: BrainLinks-BrainTools)
In their study, the scientists investigated how special types of so-called interneurons build connections with each other within the hippocampus and how their function influences the network of nerve cells as a whole. Interneurons do not prompt other nerve cells to become active but, on the contrary, inhibit them. This kind of suppression plays an important role in brain activity in general. Information processing would not be possible otherwise, because a brain in which all nerve cells are active at the same time is effectively put out of order.
The hippocampus is home to a variety of different inhibitory cells, which were known so far to differ greatly in their form and function. But up to now it has been generally assumed that their actual influence on the activity of the brain structure they belong to is rather small. By combining several different experimental methods, Bartos, Vida, and their teams succeeded in showing that these cells are actually able to strongly interfere with the activity and the timing of activity patterns within the hippocampus. Moreover, the various possible combinations of connections between these different cell types show markedly different characteristics in their function. This makes the inhibition within the hippocampus much more flexible and versatile than previously assumed. The team of scientists suspects that this also makes the capability to process information within the hippocampus much bigger. The results published in this study are from experiments conducted in acute slice preparations of the hippocampus. Up next for the researchers will be the task of verifying these results within the actual brain.
(Source: pr.uni-freiburg.de)
Rescue of Alzheimer’s Memory Deficit Achieved by Reducing ‘Excessive Inhibition’
A new drug target to fight Alzheimer’s disease has been discovered by a research team led by Gong Chen, a Professor of Biology and the Verne M. Willaman Chair in Life Sciences at Penn State University. The discovery also has potential for development as a novel diagnostic tool for Alzheimer’s disease, which is the most common form of dementia and one for which no cure has yet been found. A scientific paper describing the discovery will be published in Nature Communications on 13 June 2014.
Chen’s research was motivated by the recent failure in clinical trials of once-promising Alzheimer’s drugs being developed by large pharmaceutical companies. “Billions of dollars were invested in years of research leading up to the clinical trials of those Alzheimer’s drugs, but they failed the test after they unexpectedly worsened the patients’ symptoms,” Chen said. The research behind those drugs had targeted the long-recognized feature of Alzheimer’s brains: the sticky buildup of the amyloid protein known as plaques, which can cause neurons in the brain to die. “The research of our lab and others now has focused on finding new drug targets and on developing new approaches for diagnosing and treating Alzheimer’s disease,” Chen explained.
"We recently discovered an abnormally high concentration of one inhibitory neurotransmitter in the brains of deceased Alzheimer’s patients," Chen said. He and his research team found the neurotransmitter, called GABA (gamma-aminobutyric acid), in deformed cells called "reactive astrocytes" in a structure in the core of the brain called the dentate gyrus. This structure is the gateway to hippocampus, an area of the brain that is critical for learning and memory.
Chen’s team found that the GABA neurotransmitter was drastically increased in the deformed versions of the normally large, star-shaped “astrocyte” cells which, in a healthy individual, surround and support individual neurons in the brain. “Our research shows that the excessively high concentration of the GABA neurotransmitter in these reactive astrocytes is a novel biomarker that we hope can be targeted in further research as a tool for the diagnosis and treatment of Alzheimer’s disease,” Chen said.
Chen’s team developed new analysis methods to evaluate neurotransmitter concentrations in the brains of normal and genetically modified mouse models for Alzheimer’s disease (AD mice). “Our studies of AD mice showed that the high concentration of the GABA neurotransmitter in the reactive astrocytes of the dentate gyrus correlates with the animals’ poor performance on tests of learning and memory,” Chen said. His lab also found that the high concentration of the GABA neurotransmitter in the reactive astrocytes is released through an astrocyte-specific GABA transporter, a novel drug target found in this study, to enhance GABA inhibition in the dentate gyrus. With too much inhibitory GABA neurotransmitter, the neurons in the dentate gyrus are not fired up like they normally would be when a healthy person is learning something new or remembering something already learned.
Importantly, Chen said, “After we inhibited the astrocytic GABA transporter to reduce GABA inhibition in the brains of the AD mice, we found that they showed better memory capability than the control AD mice. We are very excited and encouraged by this result because it might explain why previous clinical trials failed by targeting amyloid plaques alone. One possible explanation is that while amyloid plaques may be reduced by targeting amyloid proteins, the other downstream alterations triggered by amyloid deposits, such as the excessive GABA inhibition discovered in our study, cannot be corrected by targeting amyloid proteins alone. Our studies suggest that reducing the excessive GABA inhibition to the neurons in the brain’s dentate gyrus may lead to a novel therapy for Alzheimer’s disease. An ultimate successful therapy may be a cocktail of compounds acting on several drug targets simultaneously.”
How brains remember and correct
Information processing in the brain is complex and involves both the processing of sensory inputs and the conversion of those inputs into behavior. The passing of electrical oscillations between networks of neurons in different parts of the brain is thought to be a critical component of cognition as well as conscious perception and awareness, but so far there has been little direct evidence linking specific neuronal oscillations to discrete thinking and behavior events.
Jun Yamamoto and colleagues from the RIKEN–MIT Center for Neural Circuit Genetics have now detected a brief burst of nerve activity oscillating in two specific parts of the mouse brain just before a correct choice is made, either when planning an action or when correcting a mistake.
The researchers searched for evidence of specific neuronal oscillations by studying mice navigating a T-shaped maze with a reward at the end of one arm of the T. Just before trained mice made the correct choice of direction, Yamamoto and his colleagues observed a brief burst of synchronized high-frequency gamma waves oscillating in specific parts of the entorhinal cortex and hippocampus.
Yamamoto was fascinated to notice that the burst of gamma waves also occurred just before mice that had originally turned in the wrong direction realized their mistake and turned round. He called this the “oops” moment, and the results indicate that similar neuronal activity occurs when making a correct choice either immediately or on realization of an error. No such gamma-wave activity was detected when mice made the wrong choice without correcting it.
To further test the link between the gamma synchrony and the memory recall process, the researchers genetically engineered mice with light-activated ion channels that could block the gamma waves. When these channels were activated, the gamma waves ceased and the mice could no longer accurately choose the right direction or correct their wrong choices.
“Our work is telling us about how the brain recalls remembered information at critical moments,” says Yamamoto. “It suggests that synchronized gamma oscillations actually contribute to the animal’s correct choice rather than being a consequence of their choice.” The finding sheds light on the fundamental mechanism underlying the successful retrieval of working memory. Yamamoto now intends to see if these initial findings apply to other brain regions.
The results also provide new insight into the phenomenon of animal consciousness. “Our findings provide evidence that animals employ a behavior monitoring process called metacognition that typically requires conscious awareness,” says Yamamoto.
Learning Early in Life May Help Keep Brain Cells Alive
Using your brain – particularly during adolescence – may help brain cells survive and could impact how the brain functions after puberty.
According to a recently published study in Frontiers in Neuroscience, Rutgers behavioral and systems neuroscientist Tracey Shors, who co-authored the study, found that the newborn brain cells in young rats that were successful at learning survived while the same brain cells in animals that didn’t master the task died quickly.
“In those that didn’t learn, three weeks after the new brain cells were made, nearly one-half of them were no longer there,” said Shors, professor in the Department of Psychology and Center for Collaborative Neuroscience at Rutgers. “But in those that learned, it was hard to count. There were so many that were still alive.”
The study is important, Shors says, because it suggests that the massive proliferation of new brain cells most likely helps young animals leave the protectiveness of their mothers and face dangers, challenges and opportunities of adulthood.
Scientists have known for years that the neurons in adult rats, which are significant but fewer in numbers than during puberty, could be saved with learning, but they did not know if this would be the case for young rats that produce two to four times more neurons than adult animals.
By examining the hippocampus – a portion of the brain associated with the process of learning – after the rats learned to associate a sound with a motor response, scientists found that the new brain cells injected with dye a few weeks earlier were still alive in those that had learned the task while the cells in those who had failed did not survive.
“It’s not that learning makes more cells,” says Shors. “It’s that the process of learning keeps new cells alive that are already present at the time of the learning experience.”
Since the process of producing new brain cells on a cellular level is similar in animals, including humans, Shors says ensuring that adolescent children learn at optimal levels is critical.
“What it has shown me, especially as an educator, is how difficult it is to achieve optimal learning for our students. You don’t want the material to be too easy to learn and yet still have it too difficult where the student doesn’t learn and gives up,” Shors says.
So, what does this mean for the 12-year-old adolescent boy or girl?
While scientists can’t measure individual brain cells in humans, Shors says this study, on the cellular level, provides a look at what is happening in the adolescent brain and provides a window into the amazing ability the brain has to reorganize itself and form new neural connections at such a transformational time in our lives.
“Adolescents are trying to figure out who they are now, who they want to be when they grow up and are at school in a learning environment all day long,” says Shors. “The brain has to have a lot of strength to respond to all those experiences.”
Scientists Find an Unlikely Stress Responder May Protect Against Alzheimer’s
In surprise findings, scientists at The Scripps Research Institute (TSRI) have discovered that a protein with a propensity to form harmful aggregates in the body when produced in the liver protects against Alzheimer’s disease aggregates when it is produced in the brain. The results suggest that drugs that can boost the protein’s production specifically in neurons could one day help ward off Alzheimer’s disease.
“This result was completely unexpected when we started this research,” said TSRI Professor Joel N. Buxbaum, MD. “But now we realize that it could indicate a new approach for Alzheimer’s prevention and therapy.”
Buxbaum and members of his laboratory report their latest finding in the May 21, 2014 issue of the Journal of Neuroscience.
First Hints
The study centers on transthyretin (TTR), a protein that is known to function as a transporter, carrying the thyroid hormone thyroxine and vitamin A through the bloodstream and cerebrospinal fluid. To do this job, it must come together in a four subunit structure called a tetramer. Certain factors such as old age and TTR gene mutations can make these tetramers prone to fall apart and misfold into tough aggregates called amyloids. TTR amyloids accumulate in the heart, kidneys, peripheral nerves and other tissues and cause life-shortening diseases including familial amyloid polyneuropathy and senile systemic (cardiac) amyloidosis.
Starting in the mid 1990s, however, reports from several laboratories hinted that TTR in the brain might protect against other amyloids—particularly the Alzheimer’s-associated protein amyloid beta. In test tube experiments, TTR seemed able to grab hold of amyloid beta and prevent it from aggregating. In transgenic “Alzheimer’s mice,” which overproduce amyloid beta, TTR expression was increased in affected brain tissue, compared to control mice, as one would expect from a protective response.
“I didn’t really believe those reports at the time,” Buxbaum said.
But he was working on TTR amyloidoses and had the tools needed to investigate the issue genetically. He and his colleagues at TSRI did those experiments, and found, to their surprise, that overproducing TTR in “Alzheimer’s mice” did indeed protect the animals: it reduced their memory deficits as well as the accumulations of amyloid beta aggregates in their brains. Since that 2008 study, Buxbaum and colleagues have gone on to publish additional experiments examining the mechanism of the protection including two last year, in collaboration with the Wright and Kelly laboratories at TSRI and Roberta Cascella in Florence, that showed how TTR tetramers can bind to amyloid beta and inhibit the latter from forming the more harmful types of aggregate.
Context Is Everything
In the latest study, Buxbaum and his team, including lead authors Xin Wang and Francesca Cattaneo, at the time both postdoctoral fellows in the Buxbaum laboratory, found another key piece of evidence for TTR’s protective role.
TTR is known to be produced principally in the liver and in the parts of the brain where cerebrospinal fluid is made. Prior studies in the Buxbaum group found evidence that TTR can also be produced in neurons, albeit at low levels. Still, it has remained unclear how TTR production, in neurons or in other cells, would be increased in response to amyloid beta accumulation.
To start, the team analyzed a segment of DNA near the TTR gene called the promoter region, where, in principle, special DNA-binding proteins called transcription factors could increase TTR gene activity. The analysis suggested that Heat Shock Factor 1 (HSF1), known as a master switch for a broad protective response against certain types of cellular stress, could bind to the TTR gene’s promoter.
Further experiments showed that HSF1 does indeed bind to this region and that two known stimulators of HSF1—heat and a compound called celastrol—also boost HSF1 binding to the TTR promoter, in addition to boosting TTR production. Remarkably, though, the researchers found that HSF1’s dialing-up of TTR production seemed to occur only in neuronal-type cells, not in liver cells where most TTR is produced.
In fact, the researchers found that in liver cells the HSF1 response somehow brought about a modest decrease in TTR production. That result may seem puzzling, but it is consistent with the idea that liver-cell TTR, which is produced at 15 to 20 times the levels of neuronal TTR, is more likely to be hazardous than protective.
Using genetic techniques to force cells to overproduce HSF1, the researchers again saw jumps in TTR gene activity and protein production, but only in neuronal cells. In liver cells TTR activity rose when HSF1 was blocked, suggesting that HSF1 normally helps keep a lid on liver TTR production.
“It’s becoming more and more evident in biology that the same molecule can do very different things in different contexts,” Buxbaum said.
To underscore the relevance to Alzheimer’s, his team examined neurons from the hippocampus brain region in ordinary lab mice and in amyloid-beta-overproducing Alzheimer’s mice. Again consistent with the concept of TTR as protective in neurons, they found that the frequency of HSF1 binding to the TTR gene promoter, and the numbers of resulting TTR gene transcripts, were both doubled in the Alzheimer’s mice compared to the ordinary lab mice.
Buxbaum and his colleagues plan to do further research on this apparent TTR-mediated stress response in neurons to determine, among other things, precisely how Alzheimer’s-associated amyloid beta switches it on. But they have already begun to think about developing a small molecule compound, suitable for delivery in a pill, that at least modestly boosts HSF1 activity and/or TTR production in neurons—and thus might prevent or delay Alzheimer’s dementia.
(Source: scripps.edu)
Cognitive test can differentiate between Alzheimer’s and normal aging
Researchers have developed a new cognitive test that can better determine whether memory impairments are due to very mild Alzheimer’s disease or the normal aging process.
Their study appears in the journal Neuropsychologia.
The Alzheimer’s Association estimates that the number of Americans living with Alzheimer’s disease will increase from 5 million in 2014 to as many as 16 million by 2050. Memory impairments and other early symptoms of Alzheimer’s are often difficult to differentiate from the effects of normal aging, making it hard for doctors to recommend treatment for those affected until the disease has progressed substantially.
Previous studies have shown that a part of the brain called the hippocampus is important to relational memory – the “ability to bind together various items of an event,” said Jim Monti, a University of Illinois postdoctoral research associate who led the work with psychology professor Neal Cohen, who is affiliated with the Beckman Institute at Illinois. Being able to connect a person’s name with his or her face is one example of relational memory. These two pieces of information are stored in different parts of the brain, but the hippocampus “binds” them so that the next time you see that person, you remember his or her name, Monti said.
Previous research has shown that people with Alzheimer’s disease often have impairments in hippocampal function. So the team designed a task that tested participants’ relational memory abilities.
Participants were shown a circle divided into three parts, each having a unique design. Similar to the process of name-and-face binding, the hippocampus works to bind these three pieces of the circle together. After the participants studied a circle, they would pick its exact match from a series of 10 circles, presented one at a time.
People with very mild Alzheimer’s disease did worse overall on the task than those in the healthy aging group, who, in turn, did worse than a group of young adults. The task also revealed an additional memory impairment unique to those with very mild Alzheimer’s disease, indicating the changes in cognition that result from Alzheimer’s are qualitatively different than healthy aging. This unique impairment allows researchers to statistically differentiate between those who did and those who did not have Alzheimer’s more accurately than some of the classical tests used for Alzheimer’s diagnosis, Monti said.
“That was illuminating and will serve to inform future work aimed at understanding and detecting the earliest cognitive manifestations of Alzheimer’s disease,” Monti said.
Although this new tool could eventually be used in clinical practice, more studies need to be done to refine the test, he said.
“We’d like to eventually study populations with fewer impairments and bring in neuroimaging techniques to better understand the initial changes in brain and cognition that are due to Alzheimer’s disease,” Monti said.
Study of neurogenesis in mice may have solved mystery of childhood amnesia in humans
A team of researchers working at the University of Toronto in Canada may have found the answer to the question of why we humans tend to have little to no memory of the first few years of our lives. In their paper published in the journal Science, the team describes several experiments they ran on mice and other small mammals that revealed the impact of neurogenesis on memory and how what they learned might be applied to memory retention in people. Lucas Mongiat and Alegandro Schinder offer a review of memory studies and how the research by the team in Toronto fits in with what has already been learned in a Perspective piece in the same journal edition.
Mouse study offers new clues to cognitive decline
New research suggests that certain types of brain cells may be “picky eaters,” seeming to prefer one specific energy source over others. The finding has implications for understanding the cognitive decline seen in aging and degenerative diseases such as Alzheimer’s and multiple sclerosis.
(Image caption: Neural stem cells differentiate into three different cell types: neurons (purple), oligodendrocytes (red), which produce axon insulation, and astrocytes (green), which also support neurons. Cell nuclei are shown in blue. Credit: Liana Roberts Stein)
Studying mice, investigators from Washington University School of Medicine in St. Louis showed that a specific energy source called NAD is important in cells responsible for maintaining the overall structure of the brain and for performing complex cognitive functions. NAD (nicotinamide adenine dinucleotide) is a molecule that harvests energy from nutrients in food and converts it into a form cells can use.
The work appears in two journal articles — in the May 8 issue of The EMBO Journal, a publication of the European Molecular Biology Organization, and in a recent issue of The Journal of Neuroscience.
“We are interested in understanding how cells make NAD and what implications that has for cellular function, especially in the context of aging and longevity,” said Shin-ichiro Imai, MD, PhD, professor of developmental biology and of medicine and senior author of both papers. “We know, for example, NAD levels decrease with age in tissues such as muscle and fat. We wanted to find out if the same is true in the brain.”
The investigators looked at two types of brain cells: adult neural stem cells, responsible for maintaining supplies of neurons and their supporting cells, and forebrain neurons, vital for performing complex cognitive tasks.
In The EMBO Journal, they reported that NAD levels decreased with age in the mouse hippocampus, a vital region of the brain for cognition. The researchers then used genetic techniques to find out what would happen when NAD manufacturing is turned off in the adult neural stem cells of the mouse brain.
“Neural stem cells are very metabolically expensive, so you might expect them to be particularly vulnerable to loss of an energy source,” said first author Liana Roberts Stein, PhD, postdoctoral researcher in Imai’s lab. “There are other energy sources for brain cells, such as glucose, but no one had ever looked at where NAD is coming from in these cells.”
According to the researchers, there are four pathways of NAD synthesis, and the scientists focused on just one. They wanted to find out whether this particular pathway — a longtime focus of Imai’s lab — is important for these cells or if the other routes could compensate.
The pathway begins with the B vitamin nicotinamide. Cells take dietary nicotinamide and, with a helper protein called Nampt, manufacture a molecule called NMN, which then is processed further to make NAD. When Stein eliminated Nampt from neural stem cells, several significant changes took place.
Levels of NAD dropped, and the neural stem cells stopped dividing; they stopped renewing themselves; and they stopped being able to create important cells that insulate axons, the “wires” that carry electrical signals throughout the brain. With less insulation, these signals slow down, impairing brain function.
Imai and Stein pointed out possible therapeutic implications of this finding, especially in light of what is known about cognitive decline in aging and certain diseases.
“Scientists have shown that with age there actually isn’t a large decrease in the total neuron population,” Stein said. “But there is quite a substantial decrease in white matter, which is primarily composed of cells that function in axon insulation. This pathway also could be relevant in conditions involving loss of cells that make this insulation, like multiple sclerosis.”
Imai and Stein also found they could prevent the loss of the neural stem cells missing Nampt by giving the mice NMN, the next molecule in the chain of events leading to NAD.
“We gave the mice NMN in their drinking water for 12 months,” Stein said. “And at the higher dose, we saw a rescue of the neural stem cell pool in aged mice.”
Imai called this finding exciting because it supports the possibility of a future NMN supplement.
“We think that NMN could convey a similar effect in people,” Imai said. “A future clinical trial for NMN will tell us if it has any efficacy in humans.”
In addition to maintaining stem cell populations and keeping the brain supplied with all its cell types, the investigators showed that NAD also is vital for the process of cognition itself.
Reporting in The Journal of Neuroscience, they showed that neurons of the mouse forebrain depend heavily on NAD in normal cognitive function. Instead of deleting Nampt in stem cells, this time Stein deleted it only in neurons of the forebrain. All other cells were normal, including those that make axon insulation.
Without Nampt and its eventual product, NAD, in forebrain neurons, the behavior of the mice changed dramatically, according to the investigators.
“The mice were really hyperactive, with a twofold increase in activity levels,” Stein said. “They also showed a loss of anxiety-like behaviors. These mice didn’t seem to sense or fear potentially threatening situations and showed fairly drastic memory defects.”
Stein pointed out that these neurons are in a region of the brain known to be particularly vulnerable to neurodegenerative conditions from Alzheimer’s disease to stroke.
“It’s possible that these neurons’ dependence on Nampt is responsible for their extreme susceptibility to these conditions,” she said. “It would be interesting to model some of these diseases in mice and see if supplementing NMN provides any benefit to their behavior or memory.”
“We haven’t done that study yet,” Imai added. “But this is the direction the entire field is going.”
(Source: news.wustl.edu)
Molecular Switches for Age-Related Memory Decline? A Genetic Variant Protects Against Brain Aging
Even among the healthiest individuals, memory and cognitive abilities decline with age. This aspect of normal aging can affect an individual’s quality of life and capability to live independently but the rate of decline is variable across individuals. There are many factors that can influence this trajectory, but perhaps none more importantly than genetics.
Scientists are seeking to identify key molecular switches that control age-related memory impairment. When new molecules are identified as critical to the process of memory consolidation, they are then tested to determine whether they contribute to the memory problems of the elderly.
One of these proteins is called KIBRA and the gene responsible for its production is WWC1. KIBRA is known to play a role in human memory and so researchers at the Lieber Institute for Brain Development and the National Institute of Mental Health, led by senior author Dr. Venkata Mattay, conducted a study to determine the effects of genetic variants in WWC1 on memory. Their findings are published in the current issue of Biological Psychiatry.
“Identifying these genetic factors, while helping us better understand the neurobiology of cognitive aging, will also aid in identifying mechanisms that confer individuals with resilience to withstand the inevitable age-related changes in neural architecture and function,” explained Mattay.
Using imaging genetics, a method that combines genetics with brain imaging technology, the team explored the effect of a variant in the WWC1 gene on age-related changes in memory function. The particular WWC1 variant under investigation has three potential forms – CC, TT, or CT.
They recruited 233 healthy volunteers, who ranged in age from 18-89 years. The volunteers completed a battery of cognitive tests, underwent genotyping, and completed a memory task during a brain imaging scan.
They found that individuals who carry the T allele, as either CT or TT, performed better on the memory task and showed more active engagement in the hippocampus, a vital brain region for memory, with increasing age.
“Our results show a dynamic relationship between this gene and increasing age on hippocampal function and episodic memory with the non-T allele group showing a significant decline across the adult life span,” said Mattay. “A similar relationship was not observed in the T-allele carrying group suggesting that this variant of the gene may confer a protective effect.”
Dr. John Krystal, Editor of Biological Psychiatry, commented, “The risk mechanisms for age-related memory impairment that we identify today may become the targets for the prevention and treatment of this problem in the future.”