Posts tagged brain

April 27, 2012

Aging may seem unavoidable, but that’s not necessarily so when it comes to the brain. So say researchers in the April 27th issue of the Cell Press journal Trends in Cognitive Sciences explaining that it is what you do in old age that matters more when it comes to maintaining a youthful brain not what you did earlier in life.

"Although some memory functions do tend to decline as we get older, several elderly show well preserved functioning and this is related to a well-preserved, youth-like brain," says Lars Nyberg of Umeå University in Sweden.

Education won’t save your brain — PhDs are as likely as high-school dropouts to experience memory loss with old age, the researchers say. Don’t count on your job either. Those with a complex or demanding career may enjoy a limited advantage, but those benefits quickly dwindle after retirement.

Engagement is the secret to success. Those who are socially, mentally and physically stimulated reliably show better cognitive performance with a brain that appears younger than its years.

"There is quite solid evidence that staying physically and mentally active is a way towards brain maintenance," Nyberg says.

The researchers say this new take on successful aging represents an important shift in focus for the field. Much attention in the past has gone instead to understanding ways in which the brain copes with or compensates for cognitive decline in aging. The research team now argues for the importance of avoiding those age-related brain changes in the first place. Genes play some role, but life choices and other environmental factors, especially in old age, are critical.

Elderly people generally do have more trouble remembering meetings or names, Nyberg says. But those memory losses often happen later than many often think, after the age of 60. Older people also continue to accumulate knowledge and to use what they know effectively, often to very old ages.

"Taken together, a wide range of findings provides converging evidence for marked heterogeneity in brain aging," the scientists write. "Critically, some older adults show little or no brain changes relative to younger adults, along with intact cognitive performance, which supports the notion of brain maintenance. In other words, maintaining a youthful brain, rather than responding to and compensating for changes, may be the key to successful memory aging."

Provided by Cell Press

Source: medicalxpress.com

April 27, 2012

(HealthDay) — Childhood socioeconomic status affects hippocampal volume in older adults, after adjusting for adult socioeconomic status, gender, education, and other factors, according to a study published in the May issue of the Annals of Neurology.

Childhood socioeconomic status affects hippocampal volume in older adults, after adjusting for adult socioeconomic status, gender, education, and other factors, according to a study published in the May issue of the Annals of Neurology.

Roger T. Staff, Ph.D., of the Aberdeen Royal Infirmary in the United Kingdom, and colleagues used magnetic resonance imaging of the brain to measure whole brain and hippocampal volume in 249 volunteers without dementia who were born in 1936. Childhood socioeconomic status history was recorded and mental ability at age 11 (recorded in 1947) was available for all participants.

After adjusting for mental ability at age 11 years, adult socioeconomic status, gender, and education, the researchers observed a significant association between childhood socioeconomic status and hippocampal volume.

"Early life socioeconomic conditions contribute to hippocampal volume in late adulthood independently of later life circumstances," the authors conclude. "These findings suggest that the capacity to compensate for age-related neuropathology (reserve) may well be established in early life."

More information: Abstract

Source: medicalxpress.com

ScienceDaily (Apr. 27, 2012) — Our genes control many aspects of who we are — from the colour of our hair to our vulnerability to certain diseases — but how are the genes, and consequently the proteins they make themselves controlled? Researchers have discovered a new group of molecules which control some of the fundamental processes behind memory function and may hold the key to developing new therapies for treating neurodegenerative diseases.

The mirror-miRNA (red) is expressed in hippocampal neurons, the nucleus is shown in blue. (Credit: Image courtesy of University of Bristol)

The research, led by academics from the University of Bristol’s Schools of Clinical Sciences, Biochemistry and Physiology & Pharmacology and published in the Journal of Biological Chemistry, has revealed a new group of molecules, called mirror-microRNAs.

MicroRNAs are non-coding genes that often reside within ‘junk DNA’ and regulate the levels and functions of multiple target proteins — responsible for controlling cellular processes in the brain. The study’s findings have shown that two microRNA genes with different functions can be produced from the same piece (sequence) of DNA — one is produced from the top strand and another from the bottom complementary ‘mirror’ strand.

Specifically, the research has shown that a single piece of human DNA gives rise to two fully processed microRNA genes that are expressed in the brain and have different and previously unknown functions. One microRNA is expressed in the parts of nerve cells that are known to control memory function and the other microRNA controls the processes that move protein cargos around nerve cells.

James Uney, Professor of Molecular Neuroscience in the University’s School of Clinical Sciences, said: “These findings are important as they show that very small changes in microRNA genes will have a dramatic effect on brain function and may influence our memory function or likelihood of developing neurodegenerative diseases. These findings also suggest that many more human mirror microRNAs will be found and that they could ultimately be used as treatments for human neurodegenerative diseases such as dementia.”

MicroRNAs can be seen as a novel regulatory layer within the genome, relying on the interaction between different RNA molecules. Through binding to messenger RNA (mRNA), they adjust the levels of proteins. Due to their small size, they are able to regulate many different RNAs. MicroRNAs have already been found throughout the double helix, lying in between genes or in areas of the code for a single gene that would normally be discarded. Such areas that were once considered “junk DNA” are now revealing a more complex and important role. In addition microRNAs can be produced in conjunction with their genes, within which they lie, or be controlled and produced entirely independently.

Helen Scott and Joanna Howarth, the lead authors on the study, added: “We have now found that both sides of the double helix can each produce a microRNA. These two microRNAs are almost a perfect mirror of each other, but due to slight differences in their sequence, they regulate different sets of protein producing RNAs, which will in turn affect different biological functions. Such mirror-miRNAs are likely to represent a new group of microRNAs with complex roles in coordinating gene expression, doubling the capacity of regulation.”

Source: Science Daily

ScienceDaily (Apr. 27, 2012) — Researchers at the Centre for Addiction and Mental Health (CAMH) led a study discovering a gene for a new form of intellectual disability, as well as how it likely affects cognitive development by disrupting neuron functioning.

CAMH Senior Scientist Dr. John Vincent and his team found a mutation in the gene NSUN2 among three sisters with intellectual disability, a finding to be published in the May issue of the American Journal of Human Genetics.

The discovery was made after mapping genes in a Pakistani family, in which three of seven siblings had intellectual disability as well as muscle weakness and walking difficulties, says Dr. Vincent, who heads the Molecular Neuropsychiatry and Development Laboratory in the Campbell Family Mental Health Research Institute at CAMH.

Intellectual disability is a condition in which individuals have limitations in their mental abilities and in functioning in daily life. It affects one to three per cent of the population, and is often caused by genetic mutations.

Another study in the same journal, submitted together with the CAMH-led research, also identified NSUN2 gene mutations in Iranian and Kurdish families with intellectual disability. As with the Pakistani family, first cousin marriages in these families carrying the mutations increased the likelihood of intellectual disability among their children, and enabled researchers to focus on areas to map genes.

"The combined results from these two studies mean that NSUN2 is among the most common causes of intellectual disability resulting from recessive genes," says Dr. Vincent.

As a recessive disorder, a child must inherit one defective NSUN2 gene from each parent to develop intellectual disability. This gene, located on chromosome 5p, encodes a type of protein called an RNA methyltransferase.

At the cellular level, the researchers found that the mutated protein was prevented from reaching its target area within the nucleus of a cell. As a result, it was unable to perform its normal role in cell division and/or RNA methylation.

Collaborators from the Wellcome Trust Centre for Stem Cell Research in Cambridge, U.K., showed which type of brain cells were likely to be most affected by this mutation. They are called Purkinje cells, a type of neuron that responds to the neurotransmitter GABA. Purkinje cells also control motor coordination, which were affected in the Pakistani family.

"We speculate that the muscle effects may result from the accumulation of the NSUN2 protein outside its target area in the nucleus," says Dr. Vincent.

To date, Dr. Vincent’s lab has identified five genes causing different forms of recessive intellectual disability.

Source: Science Daily

ScienceDaily (Apr. 26, 2012) — A new University of British Columbia study finds that analytic thinking can decrease religious belief, even in devout believers.

The statue “The Thinker,” by Auguste Rodin. (Credit: © Ignatius Wooster / Fotolia)

The study, which is published in the April 27 issue of Science, finds that thinking analytically increases disbelief among believers and skeptics alike, shedding important new light on the psychology of religious belief.

“Our goal was to explore the fundamental question of why people believe in a God to different degrees,” says lead author Will Gervais, a PhD student in UBC’s Dept. of Psychology. “A combination of complex factors influence matters of personal spirituality, and these new findings suggest that the cognitive system related to analytic thoughts is one factor that can influence disbelief.”

Researchers used problem-solving tasks and subtle experimental priming – including showing participants Rodin’s sculpture The Thinker or asking participants to complete questionnaires in hard-to-read fonts – to successfully produce “analytic” thinking. The researchers, who assessed participants’ belief levels using a variety of self-reported measures, found that religious belief decreased when participants engaged in analytic tasks, compared to participants who engaged in tasks that did not involve analytic thinking.

The findings, Gervais says, are based on a longstanding human psychology model of two distinct, but related cognitive systems to process information: an “intuitive” system that relies on mental shortcuts to yield fast and efficient responses, and a more “analytic” system that yields more deliberate, reasoned responses.

“Our study builds on previous research that links religious beliefs to ‘intuitive’ thinking,” says study co-author and Associate Prof. Ara Norenzayan, UBC Dept. of Psychology. “Our findings suggest that activating the ‘analytic’ cognitive system in the brain can undermine the ‘intuitive’ support for religious belief, at least temporarily.”

The study involved more than 650 participants in the U.S. and Canada. Gervais says future studies will explore whether the increase in religious disbelief is temporary or long-lasting, and how the findings apply to non-Western cultures.

Recent figures suggest that the majority of the world’s population believes in a God, however atheists and agnostics number in the hundreds of millions, says Norenzayan, a co-director of UBC’s Centre for Human Evolution, Cognition and Culture. Religious convictions are shaped by psychological and cultural factors and fluctuate across time and situations, he says.

Source: Science Daily

ScienceDaily (Apr. 26, 2012) — Scientists at the Gladstone Institutes have unraveled a process by which depletion of a specific protein in the brain contributes to the memory problems associated with Alzheimer’s disease. These findings provide insights into the disease’s development and may lead to new therapies that could benefit the millions of people worldwide suffering from Alzheimer’s and other devastating neurological disorders.

The study, led by Gladstone Investigator Jorge J. Palop, PhD, revealed that low levels of a protein, called Nav1.1, disrupt the electrical activity between brain cells. Such activity is crucial for healthy brain function and memory. Indeed, the researchers found that restoring Nav1.1 levels in mice that were genetically modified to mimic key aspects of Alzheimer’s disease (AD-mice) improved learning and memory functions and increased their lifespan. Their findings are featured on the cover of the April 27 issue of Cell, available online April 26.

"It is estimated that more than 30 million people worldwide suffer from Alzheimer’s disease and that number is expected to rise dramatically in the near future," said Lennart Mucke, MD, who directs neurological research at Gladstone, an independent and nonprofit biomedical-research organization. "This research improves our understanding of the biological processes that underlie cognitive dysfunction in this disease and could open the door for new therapeutic interventions."

The researchers’ findings suggest that Nav1.1 levels in special regulatory nerve cells called parvalbumin cells, or PV cells, are essential to generate healthy brain-wave activity — and that problems in this process contribute to cognitive decline in AD-mice and possibly in patients with Alzheimer’s.

In the brain, neurons form highly interconnected networks, using chemical and electrical signals to communicate with each other. The researchers investigated whether this communication between neurons is disrupted in AD-mice, and if so, how this may affect the symptoms of Alzheimer’s disease.

To study this, they performed electroencephalogram (EEG) recordings — a technique that detects abnormalities in the brain’s electrical waves such as those found in patients with epilepsy. They found that similar abnormalities emerged during periods of reduced gamma-wave oscillations — a type of brain wave that is crucial to regulating learning and memory.

"Like a conductor in an orchestra, PV cells regulate brain rhythms by precisely controlling excitatory brain activity," said Laure Verret, PhD, postdoctoral fellow and lead author. "We found that PV cells in patients with Alzheimer’s and in AD-mice have low levels of the protein Nav1.1 — likely contributing to PV cell dysfunction. As a consequence, AD-mice had abnormal brain rhythms. By restoring Nav1.1 levels, we were able to re-establish normal brain function."

Indeed, the scientists found that increasing Nav1.1 levels in PV cells improves brain wave activity, learning, memory and survival rates in AD-mice.

"Enhancing Nav1.1 activity, and consequently improving PV cell function, may help in the treatment of Alzheimer’s disease and other neurological disorders associated with gamma-wave alterations and cognitive impairments such as epilepsy, autism and schizophrenia," said Dr. Palop, who is also an assistant professor of neurology at the University of California, San Francisco, with which Gladstone is affiliated. "These findings may allow us to develop therapies to help patients with these devastating diseases."

Source: Science Daily

ScienceDaily (Apr. 26, 2012) — The ability to navigate using spatial cues was impaired in mice whose brains were minus a channel that delivers potassium — a finding that may have implications for humans with damage to the hippocampus, a brain structure critical to memory and learning, according to a Baylor University researcher.

Mice missing the channel also showed diminished learning ability in an experiment dealing with fear conditioning, said Joaquin Lugo, Ph.D., the lead author in the study and an assistant professor of psychology and neuroscience in Baylor’s College of Arts & Sciences. “By targeting chemical pathways that alter those potassium channels, we may eventually be able to apply the findings to humans and reverse some of the cognitive deficits in people with epilepsy and other neurological disorders,” Lugo said.

The research was done in Baylor College of Medicine Intellectual and Developmental Disabilities Research Center Mouse Neurobehavior Core in Houston during Lugo’s time as a researcher there.

The findings are published online in the journal Learning & Memory.

The channel, called Kv4.2, delivers potassium, which aids neuron function in the brain’s hippocampus. The hippocampus forms memory for long-term storage in the brain. Potassium also helps to regulate excitability.

Individuals who have epilepsy sometimes exhibit altered or missing Kv.4.2 channels or similar types of channels.

In the experiment investigating navigation, “knockout” mice — those without the channel — were tested in a water maze four feet in diameter and 12 inches deep, with eight trials daily — each lasting about a minute — over four days, he said. Their performance was compared with that of normal mice.

Both groups responded to visual cues — colored symbols — in learning their way around the maze, but the knockout mice did not respond as well as the normal mice in terms of spatial cues — hidden platforms in the water.

"When the mice don’t have this channel, it hurts their ability to learn," Lugo said. In a separate experiment examining fear conditioning, both knockout mice and normal mice were placed in a cage, and researchers sounded a tone before giving the mice a mild electric shock. In repeated trials, both groups began to freeze upon hearing the tone as they anticipated a shock. But the normal mice also reacted to the context — being placed in the cage — while the mice who did not have the Kv4.2 channel reacted only to the tone. The research was funded by the Epilepsy Foundation and the National Institutes of Health.

Source: Science Daily

ScienceDaily (Apr. 26, 2012) — They say you can’t teach an old dog new tricks. Fortunately, this is not always true. Researchers at the Netherlands Institute for Neuroscience (NIN-KNAW) have now discovered how the adult brain can adapt to new situations. The Dutch researchers’ findings are published on April 25 in the journal Neuron. Their study may be significant in developing treatments of neurodevelopmental disorders.

Two inhibitory synapses (yellow) disappear from the process of a nerve-cell (red) during learning. (Credit: Image courtesy of Netherlands Institute for Neuroscience)

Ability to learn

Our brain processes information in complex networks of nerve cells. The cells communicate and excite one another through special connections, called synapses. Young brains are capable of forming many new synapses, and they are consequently better at learning new things. That is why we acquire vital skills — walking, talking, hearing and seeing — early on in life. The adult brain stabilises the synapses so that we can use what we have learned in childhood for the rest of our lives.

Disappearing inhibitors

Earlier research found that approximately one fifth of the synapses in the brain inhibit rather than excite other nerve-cell activity. Neuroscientists have now shown that many of these inhibitory synapses disappear if the adult brain is forced to learn new skills. They reached this conclusion by labelling inhibitory synapses in mouse brains with fluorescent proteins and then tracking them for several weeks using a specialised microscope. They then closed one of the mice’s eyes temporarily to accustom them to seeing through just one eye. After a few days, the area of the brain that processes information from both eyes began to respond more actively to the open eye. At the same time, many of the inhibitory synapses disappeared and were later replaced by new synapses.

Regulating the information network

Inhibitory synapses are vital for the way networks function in the brain. “Think of the excitatory synapses as a road network, with traffic being guided from A to B, and the inhibitory synapses as the matrix signs that regulate the traffic,” explains research leader Christiaan Levelt. “The inhibitory synapses ensure an efficient flow of traffic in the brain. If they don’t, the system becomes overloaded, for example as in epilepsy; if they constantly indicate a speed of 20 kilometres an hour, then everything will grind to a halt, for example when an anaesthetic is administered. If you can move the signs to different locations, you can bring about major changes in traffic flows without having to entirely reroute the road network.”

Hope

Inhibitory synapses play a hugely influential role on learning in the young brain. People who have neurodevelopmental disorders — for example epilepsy, but also autism and schizophrenia — may have trouble forming inhibitory synapses. The discovery that the adult brain is still capable of pruning or forming these synapses offers hope that pharmacological or genetic intervention can be used to enhance or manage this process. This could lead to important guideposts for treating the above-mentioned neurological disorders, but also repairing damaged brain tissue.

Source: Science Daily

April 26, 2012

They say you can’t teach an old dog new tricks. Fortunately, this is not always true. Researchers at the Netherlands Institute for Neuroscience have now discovered how the adult brain can adapt to new situations. The Dutch researchers’ findings are published on Wednesday in the prestigious journal Neuron. Their study may be significant in the treatment of neurodevelopmental disorders such as epilepsy, autism and schizophrenia.

Our brain processes information in complex networks of nerve cells. The cells communicate and excite one another through special connections, called synapses. Young brains are capable of forming many new synapses, and they are consequently better at learning new things. That is why we acquire vital skills – walking, talking, hearing and seeing – early on in life. The adult brain stabilises the synapses so that we can use what we have learned in childhood for the rest of our lives.

Earlier research found that approximately one fifth of the synapses in the brain inhibit rather than excite other nerve-cell activity. Neuroscientists have now shown that many of these inhibitory synapses disappear if the adult brain is forced to learn new skills. They reached this conclusion by labelling inhibitory synapses in mouse brains with fluorescent proteins and then tracking them for several weeks using a specialised microscope. They then closed one of the mice’s eyes temporarily to accustom them to seeing through just one eye. After a few days, the area of the brain that processes information from both eyes began to respond more actively to the open eye. At the same time, many of the inhibitory synapses disappeared and were later replaced by new synapses.

Inhibitory synapses are vital for the way networks function in the brain. “Think of the excitatory synapses as a road network, with traffic being guided from A to B, and the inhibitory synapses as the matrix signs that regulate the traffic,” explains research leader Christiaan Levelt. “The inhibitory synapses ensure an efficient flow of traffic in the brain. If they don’t, the system becomes overloaded, for example as in epilepsy; if they constantly indicate a speed of 20 kilometres an hour, then everything will grind to a halt, for example when an anaesthetic is administered. If you can move the signs to different locations, you can bring about major changes in traffic flows without having to entirely reroute the road network.”

Inhibitory synapses play a hugely influential role on learning in the young brain. People who have neurodevelopmental disorders – for example epilepsy, but also autism and schizophrenia – may have trouble forming inhibitory synapses. The discovery that the adult brain is still capable of pruning or forming these synapses offers hope that pharmacological or genetic intervention can be used to enhance or manage this process. This could lead to important guideposts for treating the above-mentioned neurological disorders, but also repairing damaged brain tissue.

Provided by Royal Netherlands Academy of Arts and Sciences

Source: medicalxpress.com

April 26, 2012

What happens at the level of individual neurons while we learn? This question intrigued the neuroscientist Daniel Huber, who recently arrived at the Department of Basic Neuroscience at the University of Geneva. During his stay in the United States, he and his team tried to unravel the network mechanisms underlying learning and memory at the level of the cerebral cortex.

What’s the role of individual neurons in behavior? Do they always participate in the same functions? How do their responses evolve during learning?” asks the professor. One way to address these questions is to follow the activity of a large set of neurons while the subject learns a novel task. The goal is to link the behavioral changes with the changes in neuronal representations.

It’s currently impossible to follow the activity of a large number of individual neurons in humans, but the team of researchers quickly realized that mice are excellent subjects for such studies. “We were surprised by capacities of these small rodents. They learn novel associations quickly and are able to focus for hours on complex behavioral tasks. However, it is important to keep them motivated by rewarding them accordingly. They are very similar to us in that way.”

The behavioral task of the mice consisted in sampling the area in front of their snout with their whiskers to search for a small object. The object was presented either within reach and out of reach of their whiskers. Each time the object was detected with the whiskers, the mouse had to respond by licking to a reward spout. The correct choices were rewarded with a drop of liquid. “In this task different sensory and motor circuits have to interact in order to establish a novel association, leading to better and better performance”.

Remained the problem of how to follow the activity of the large number of neurons across many days of learning. The researchers replaced a small part of the bone overlying motor cortex with a tiny glass window. The neurons underneath the window were genetically modified to express a fluorescent marker which changes its intensity according to the activity of the neurons. This window into the brain allowed the researches around Daniel Huber to use two-photon microscopy to record the activity of the same set of 500 neurons during days of learning. 

"We then correlated the activity of the individual neurons with the different actions of the mouse, such as moving the whiskers, touching the object or licking at the right moment. It’s like synchronizing the soundtrack with the images in a movie" adds the neuroscientist. The researchers analyzed this data using a series of computational approaches to establish a link between the neuronal activity and the different sensory and motor features of the task. This allowed them to build algorithmic models that can predict different motor outputs by solely monitoring the neuronal activity. Decoding the neuronal activity allowed the researchers then to construct functional maps of the recorded neurons and quantify each neuron’s link with the different aspects of the behavior.

These functional maps revealed several fundamental findings: “Although the movements of the whiskers became more and more precise and targeted to search for the object during the learning, their relative neuronal representation remained relatively stable. In contrast, the representation of licking to respond and collect the rewards became more and more pronounced”. Taken together, only selected aspects of the learned behavior induced changes it the neuronal representation in the cortex. The scientists also found that different sensory and motor representations are spatially intermingled in the rodent brain.

Other analysis revealed that individual neurons remain stably linked to a given behavioral function, but they have a flexibility to remain silent on a given day. This functional stability despite a flexibility to join (or not) a given representation was actually suggested by different theoretical work on learning.

"If these characteristics are limited to the motor cortex or if these are more general rules that are apply across the cerebral cortex remains open" says Daniel Huber. That in fact this is one of the questions we are currently investigating in my lab in Geneva".

Provided by University of Geneva

Source: medicalxpress.com