Posts tagged science

May 10, 2012

(Medical Xpress) — A new mathematical model predicting how nerve fibres make connections during brain development could aid understanding of how some cognitive disorders occur.

The model, constructed by scientists at the Queensland Brain Institute (QBI) and School of Mathematics and Physics at the University of Queensland (UQ), gives new insight into how changing chemical levels in nerve fibres can modify nerve wiring underpinning connections in the brain.

Professor Geoff Goodhill says that while scientists have long known that changing these chemical levels can change where nerve fibres grow, only now are they understanding why this is the case.

“Our mathematical model allows us to predict precisely how these chemical levels control the direction in which nerve fibres grow, during both neural development and regeneration after injury,” he said.

Correct brain wiring is fundamental for normal brain function.

Recent discoveries suggest that wiring problems may underpin a number of nervous system disorders including autism, dyslexia, Down syndrome, Tourette’s syndrome and Parkinson’s disease.

The new model, published in the prestigious cell journal Neurondemonstrates the important role mathematics can play in understanding how the brain develops, and perhaps ultimately preventing such disorders. 

Provided by University of Queensland 

Source: medicalxpress.com

May 10, 2012

(Medical Xpress) — Scientists at University of Queensland’s Brain Institute are one step closer to developing new therapies for treating dementia.

QBI’s Dr Jana Vukovic said the work was aimed at understanding the molecular mechanism that may impair learning and memory in the ageing population.

“Ageing slows the production of new nerve cells, reducing the brain’s ability to form new memories,” said Dr Vokovic, who performed the work in the laboratory of Professor Perry Bartlett, the Director of QBI at The University of Queensland.

"But our research shows for the first time that the brain cells usually responsible for mediating immunity, microglia, have an inhibitory effect on memory during ageing.

“Furthermore, they have shown that a molecule produced by nerve cells, fractalkine, can reverse this process and stimulate stem cells to produce new neurons.”

The discovery, published in The Journal of Neuroscience today, came after QBI scientists observed that the increased production of new neurons in mice that were actively running was due to the release of fractalkine in the hippocampus – the brain structure responsible for specific types of learning and memory.

Professor Bartlett said it had been known for some time that exercise increased the production of new nerve cells in the hippocampus in young and even aged mice.

“But this study found that it is fractalkine that appears to be specifically mediating this effect by making the microglia produce factors that activate the stem cells that produce new nerve cells,” he said.

“Once the cells are activated they divide and produce new cells, which underpin the animal’s ability to learn and form memories.

"This means that fractalkine may form the basis for the development of future therapies.

“The discovery is especially exciting because we have found that older animals suffering cognitive decline showed significantly lower levels of fractalkine.

“We are seeking ways of increasing fractalkine levels in patients with cognitive decline, and hoping this may be a new frontline therapy in treating dementia.”

Dr Vukovic said that until relatively recently, it was thought the adult brain was incapable of generating new neurons.

“But work from Professor Bartlett’s laboratory over the past 20 years has demonstrated that the brains of adult animals, including humans, retain the ability to make new nerve cells,” she said.

“The challenge is to find out how to stimulate this production in the aged animal and human where production has slowed.”

The latest work was a significant step toward achieving this goal, she said.

Provided by University of Queensland

Source: medicalxpress.com

May 10, 2012

(Medical Xpress) — How do we build a memory in the brain? It is well known that for animals (and humans) new proteins are needed to establish long-term memories. During learning information is stored at the synapses, the junctions connecting nerve cells. Synapses also require new proteins in order to show changes in their strength (synaptic plasticity). Historically, scientists have focused on the cell body as the place where the required proteins are synthesized. However, in recent years there has been increasing focus on the dendrites and axons (the compartments that meet to form synapses) as a potential site for protein synthesis.

Protein synthesis machines have been observed there as well as a limited number of their templates, the messenger RNA molecules. The limited number of mRNAs observed in dendrites and axons placed constraints on the constellation of proteins that could be synthesized to help synapses work and change. Researchers from Erin Schuman’s lab at the Max Planck Institute (MPI) for Brain Research used new-generation sequencing to directly identify a very large number (over 2500) of new mRNA molecules that are present at the axons and dendrites. Using high-resolution imaging techniques they were able to both quantify and visualize individual mRNA molecules. They published their findings in the latest issue of Neuron.

[Video]
Erin Schuman and her colleagues describe how they were able to detect numerous new mRNAs in the processes of neurons with unprecedented sensitivity. Video: Neuron.

Using microarray approaches and/or in situ hybridization techniques, many different groups had each identified a hundred or so mRNAs that might reside in the dendrites. By analyzing and comparing these studies the Schuman team discovered something surprising: it seems that not a single mRNA type was found in all three studies. This observation made the scientist at the MPI for Brain Research wonder whether the already discovered mRNAs are just the tip of the iceberg and whether there were many more mRNA molecules waiting to be discovered.

In order to find out the researchers dissected the neuropil layer of the rat hippocampus. This layer comprises a high concentration of axons and dendrites, but lacks the cell bodies of pyramidal neurons (the principal cell type in the hippocampus and other brain areas). By using sensitive high-resolution sequencing techniques, mRNAs could be detected which, due to their lower concentrations, were not discovered before. The researchers found an impressive number of 2550 unique mRNAs present at the dendrites and/or axons. To determine the relative abundance in the neuronal cells, the scientists at Erin Schuman’s lab used the Nanostring nCounter, a new technique allowing the high-resolution visualization and quantification of single mRNA molecules. They found that the concentration of mRNAs in the euronal cells varies by three orders of magnitude. Additionally, the researchers were able to classify many of the mRNAs and determine their function in synaptic plasticity. These include signaling molecules, scaffolds and the receptors for neurotransmitter molecules. In addition, many mRNAs coding for protein implicated in diseases like autism were discovered in the dendrites and axons. Finally, by using advanced imaging techniques, the researchers could directly visualize some of the mRNAs in the neuronal dendrites, hundreds of micrometers from the cell body.

These results reveal a previously unappreciated enormous potential for the local protein synthesis machinery to supply, maintain and modify the dendritic and synaptic protein population. It seems that neurons use a local control mechanism much in the same way that modern societies have learned that the most efficient means to distribute goods to the population is to use local distribution centers.

Provided by Max Planck Society

Source: medicalxpress.com

May 9, 2012 

Efforts to understand how the aging process affects the brain and cognition have expanded beyond simply comparing younger and older adults.

"Everybody ages differently. By looking at genetic variations and individual differences in markers of vascular health, we begin to understand that preventable factors may affect our chances for successful aging," said Wayne State University psychology doctoral student Andrew Bender, lead author of a study supported by the National Institute on Aging of the National Institutes of Health and now in press in the journal Neuropsychologia.

The report, “Age-related Differences in Memory and Executive Functions in Healthy APOE ε4 Carriers: The Contribution of Individual Differences in Prefrontal Volumes and Systolic Blood Pressure,” focuses on carriers of the ε4 variant of the apolipoprotein (APOE) gene, present in roughly 25 percent of the population. Compared to those who possess other forms of the APOE gene, carriers of the ε4 allele are at significantly greater risk for Alzheimer’s, dementia and cardiovascular disease.

Many studies also have shown that nondemented carriers of the APOE ε4 variant have smaller brain volumes and perform less well on cognitive tests than carriers of other gene variants. Those findings, however, are not consistent, and a possible explanation may come from examining interactions between the risky genes and other factors, such as markers of cardiovascular health. Prior research in typical samples of older adults has shown that indeed other vascular risk factors — such as elevated cholesterol, hypertension or diabetes — can exacerbate the impact of the APOE ε4 variant on brain and cognition, but it is unclear if such synergy of risks is present in healthy adults.

Thus, Wayne State researchers evaluated a group of volunteers from 19 to 77 years of age who self-reported as exceptionally healthy on a questionnaire that screened for a number of conditions, representing a “best case scenario” of healthy aging. The research project, led by Naftali Raz, Ph.D., professor of psychology and director of the Lifespan Cognitive Neuroscience Research Program at WSU’s Institute of Gerontology, tested different cognitive abilities known for their sensitivity to aging and the effects of the APOE ε4 variant. Those abilities include speed of information processing, working memory (holding and manipulating information in one’s mind) and episodic memory (memory for events).

Researchers also measured participants’ blood pressure, performed genetic testing to determine which APOE variant participants carried, and measured the volumes of several critical brain regions using a high-resolution structural magnetic resonance imaging brain scan. Bender and Raz showed that for older APOE ε4 carriers, even minor increases in systolic blood pressure (the higher of the two numbers that are reported in blood pressure measures) were linked with smaller volumes of the prefrontal cortex and prefrontal white matter, slower speed of information processing, reduced working memory capacity and worse verbal memory. Notably, they said, that pattern was not evident in those who lacked the ε4 gene variant.

The study concludes that the APOE ε4 gene may make its carriers sensitive to negative effects of relatively subtle elevations in systolic blood pressure, and that the interplay between two risk factors, genetic and physiological, is detrimental to the key brain structures and associated cognitive functions.

"Although genes play a significant role in shaping the effects of age and vascular risk on the brain and cognition, the impact of single genetic variants is relatively small, and there are quite a few of them. Thus, one’s aging should not be seen through the lens of one’s genetic profile," cautioned the study’s authors. They continued, "The negative impact of many genetic variations needs help from other risk factors, and while there isn’t much one can do about genes, a lot can be done about vascular risk factors such as blood pressure or cholesterol."

"Everybody should try to keep those in check, although people with certain genetic variants more so than others." Raz said. "Practically speaking, even with the best deck of genetic cards dealt to you, it still makes sense to reduce risk through whatever works: exercise, diet or, if those fail, medication."

Because the study is part of a longitudinal project, he and Bender said the immediate future task now is to determine how the interaction between risky genes and vascular risk factors affect the trajectory of age-related changes — not differences, as in this cross-sectional study — in brain and cognition.

Provided by Wayne State University

Source: medicalxpress.com

May 9, 2012

Chronic exposure to cocaine reduces the expression of a protein known to regulate brain plasticity, according to new, in vivo research on the molecular basis of cocaine addiction. That reduction drives structural changes in the brain, which produce greater sensitivity to the rewarding effects of cocaine.

The research, led by UB’s Dietz, suggests a potential new target for development of a treatment for cocaine addiction. Credit: Douglas Levere, UB Communications

The finding suggests a potential new target for development of a treatment for cocaine addiction. It was published last month in Nature Neuroscience by researchers at the University at Buffalo and Mount Sinai School of Medicine.

"We found that chronic cocaine exposure in mice led to a decrease in this protein’s signaling," says David Dietz, PhD, assistant professor of pharmacology and toxicology in the School of Medicine and Biomedical Sciences, who did the work while at Mt. Sinai. "The reduction of the expression of the protein, called Rac1, then set in motion a cascade of events involved in structural plasticity of the brain — the shape and growth of neuronal processes in the brain. Among the most important of these events is the large increase in the number of physical protrusions or spines that grow out from the neurons in the reward center of the brain.

"This suggests that Rac1 may control how exposure to drugs of abuse, like cocaine, may rewire the brain in a way that makes an individual more susceptible to the addicted state," says Dietz.

The presence of the spines demonstrates the spike in the reward effect that the individual obtains from exposure to cocaine. By changing the level of expression of Rac1, Dietz and his colleagues were able to control whether or not the mice became addicted, by preventing enhancement of the brain’s reward center due to cocaine exposure.

To do the experiment, Dietz and his colleagues used a novel tool, which allowed for light activation to control Rac1 expression, the first time that a light-activated protein has been used to modulate brain plasticity.

"We can now understand how proteins function in a very temporal pattern, so we could look at how regulating genes at a specific time point could affect behavior, such as drug addiction, or a disease state," says Dietz.

In his UB lab, Dietz is continuing his research on the relationship between behavior and brain plasticity, looking, for example, at how plasticity might determine how much of a drug an animal takes and how persistent the animal is in trying to get the drug.

Provided by University at Buffalo

Source: medicalxpress.com

May 9, 2012

While we often think of memory as a way of preserving the essential idea of who we are, little thought is given to the importance of forgetting to our wellbeing, whether what we forget belongs in the “horrible memories department” or just reflects the minutia of day-to-day living.

Despite the fact that forgetting is normal, exactly how we forget—the molecular, cellular, and brain circuit mechanisms underlying the process—is poorly understood.

Now, in a study that appears in the May 10, 2012 issue of the journal Neuron, scientists from the Florida campus of The Scripps Research Institute have pinpointed a mechanism that is essential for forming memories in the first place and, as it turns out, is equally essential for eliminating them after memories have formed.

"This study focuses on the molecular biology of active forgetting," said Ron Davis, chair of the Scripps Research Department of Neuroscience who led the project. "Until now, the basic thought has been that forgetting is mostly a passive process. Our findings make clear that forgetting is an active process that is probably regulated."

The Two Faces of Dopamine

To better understand the mechanisms for forgetting, Davis and his colleagues studied Drosophila or fruit flies, a key model for studying memory that has been found to be highly applicable to humans. The flies were put in situations where they learned that certain smells were associated with either a positive reinforcement like food or a negative one, such as a mild electric shock. The scientists then observed changes in the flies’ brains as they remembered or forgot the new information.

The results showed that a small subset of dopamine neurons actively regulate the acquisition of memories and the forgetting of these memories after learning, using a pair of dopamine receptors in the brain. Dopamine is a neurotransmitter that plays an important role in a number of processes including punishment and reward, memory, learning and cognition.

But how can a single neurotransmitter, dopamine, have two seemingly opposite roles in both forming and eliminating memories? And how can these two dopamine receptors serve acquiring memory on the one hand, and forgetting on the other?

The study suggests that when a new memory is first formed, there also exists an active, dopamine-based forgetting mechanism—ongoing dopamine neuron activity—that begins to erase those memories unless some importance is attached to them, a process known as consolidation that may shield important memories from the dopamine-driven forgetting process.

The study shows that specific neurons in the brain release dopamine to two different receptors known as dDA1 and DAMB, located on what are called mushroom bodies because of their shape; these densely packed networks of neurons are vital for memory and learning in insects. The study found the dDA1 receptor is responsible for memory acquisition, while DAMB is required for forgetting.

When dopamine neurons begin the signaling process, the dDA1 receptor becomes overstimulated and begins to form memories, an essential part of memory acquisition. Once that memory is acquired, however, these same dopamine neurons continue signaling. Except this time, the signal goes through the DAMB receptor, which triggers forgetting of those recently acquired, but not yet consolidated, memories.

Jacob Berry, a graduate student in the Davis lab who led the experimentation, showed that inhibiting the dopamine signaling after learning enhanced the flies’ memory. Hyperactivating those same neurons after learning erased memory. And, a mutation in one of the receptors, dDA1, produced flies unable to learn, while a mutation in the other, DAMB, blocked forgetting.

Intriguing Issues

While Davis was surprised by the mechanisms the study uncovered, he was not surprised that forgetting is an active process. “Biology isn’t designed to do things in a passive way,” he said. “There are active pathways for constructing things, and active ones for degrading things. Why should forgetting be any different?”

The study also brings into a focus a lot of intriguing issues, Davis said—savant syndrome, for example.

"Savants have a high capacity for memory in some specialized areas," he said. "But maybe it isn’t memory that gives them this capacity, maybe they have a bad forgetting mechanism. This also might be a strategy for developing drugs to promote cognition and memory—what about drugs that inhibit forgetting as cognitive enhancers?"

Provided by The Scripps Research Institute

Source: medicalxpress.com

ScienceDaily (May 9, 2012) — In sports, on a game show, or just on the job, what causes people to choke when the stakes are high? A new study by researchers at the California Institute of Technology (Caltech) suggests that when there are high financial incentives to succeed, people can become so afraid of losing their potentially lucrative reward that their performance suffers.

In the study, each participant was asked to control this virtual object on a screen. The virtual object consisted of two weighted balls connected by a spring. The task was to place the object, which stretched and contracted as a weighted spring would in real life, into a square target within two seconds. (Credit: Image courtesy of California Institute of Technology)

It is a somewhat unexpected conclusion. After all, you would think that the more people are paid, the harder they will work, and the better they will do their jobs — until they reach the limits of their skills. That notion tends to hold true when the stakes are low, says Vikram Chib, a postdoctoral scholar at Caltech and lead author on a paper published in the May 10 issue of the journalNeuron. Previous research, however, has shown that if you pay people too much, their performance actually declines.

Some experts have attributed this decline to too much motivation: they think that, faced with the prospect of earning an extra chunk of cash, you might get so excited that you will fail to do the task properly. But now, after looking at brain-scan data of volunteers performing a specific motor task, the Caltech team says that what actually happens is that you become worried about losing your potential prize. The researchers also found that the more someone is afraid of loss, the worse they perform.

In the study, each participant was asked to control a virtual object on a screen by moving an index finger that had a tracking device attached to it. The virtual object consisted of two weighted balls connected by a spring. The task was to place the object, which stretched and contracted as a weighted spring would in real life, into a square target within two seconds.

The researchers controlled for individual skill levels by customizing the size of the target so that everyone would have the same success rate. That way, people who happened to be really good or bad at this task would not skew the data.

After a training period, the subjects were asked to perform the task while inside an fMRI machine, which measures blood flow in the brain — a proxy for brain activity, since wherever a brain is active, it needs extra oxygen, and thus a larger volume of blood. By monitoring blood flow, the researchers can pinpoint areas of the brain that turn on when a particular task is performed.

The task began with the researchers offering the participants a randomized range of rewards — from $0 to $100 — if they could successfully place the object into the square within the time limit. At the end of hundreds of trials — each with varying reward amounts — the participant was given their reward, based on the result of just one of the trials, picked at random.

As expected, the team found that performance improved as the incentives increased — but only when the cash reward amounts were at the low end of the spectrum. Once the rewards passed a certain threshold, which depended on the individual, performance began to fall off.

Incentives are known to activate a part of your brain called the ventral striatum, Chib says; the researchers thus expected to see the ventral striatum become increasingly active as they bumped up the prizes. And if the conventional thought were correct — that the reason for the observed performance decline was over-motivation — they would expect the striatum to continue showing a lot of activation when the incentives became high enough for performance to suffer.

What they found, instead, was that when the participants were shown their potential rewards, activity in the striatum did indeed increase with rising incentives. But once the volunteers started doing the task, striatal activity decreased with rising incentives. They also noticed that the less activity they saw in a participant’s striatum, the worse that person performed on the task.

Other studies have shown that decreasing striatal activity is related to fear or aversion to loss, Chib says. “When people see the incentive that they’re being offered, they initially encode it as a gain,” he explains. “But when they’re actually doing the task, the thing that causes them to perform poorly is that they worry about losing a potential incentive they haven’t even received yet.” He adds, “We’re showing loss aversion even though there are no explicit losses anywhere in the task — that’s very strange and something you really wouldn’t expect.”

To further test their hypothesis, Chib and his colleagues decided to measure how loss-averse each participant was. They had the participants play a coin-flip game in which there was an equal chance they could win or lose varying amounts of money.

Each participant was offered varying potential win-loss amounts ($20-$20, $20-$10, $20-$5, for example), and then given the opportunity to either accept each possible gamble or decline it. The win-loss ratio at which the subjects chose to take the gamble provided a measure of how loss-averse each person was; someone willing to gamble even when they might win or lose $20 is less loss-averse than someone who is only willing to gamble if they can win $20 but only lose $5.

Once the numbers had been crunched and compared to the original experiment, it turned out that the more averse a participant was, the worse they did on the task when the stakes were high. And for a particularly loss-aversive person, the threshold at which their performance started to decline did not have to be very high. “If you’re more loss-averse, it really hurts you,” Chib says. “You’re going to reach peak performance at a lower incentive level, and your performance is also going to be worse for higher incentives.”

"Previously, it’s been shown that the ventral striatum is involved in mediating performance increases in response to rising incentives," says John O’Doherty, professor of psychology and coauthor of the paper. "But our study shows that changes in activity in this same region can, under certain situations, also lead to worsening performance."

While this study only involved a specific motor task and financial incentives, these results may well be universal, says Shinsuke Shimojo, the Gertrude Baltimore Professor of Experimental Psychology and another coauthor of the study. “The implications and applications can include any sort of decision making that contains high stakes and uncertainties, such as business and politics.”

These findings, the researchers say, might be used to develop new ways to motivate people to perform better or to train them to be less loss-averse. “This loss aversion can be an important way of deciding how to set up incentive mechanisms and how to figure out who’s going to perform well and who isn’t,” Chib says. “If you can train somebody to be less loss-averse, maybe you can help them avoid performing poorly in stressful situations.”

Source: Science Daily

May 9, 2012

How well people with newly diagnosed epilepsy respond to their first drug treatment may signal the likelihood that they will continue to have more seizures, according to a study published in the May 9, 2012, online issue ofNeurology, the medical journal of the American Academy of Neurology.

"Our research shows a pattern based on how a person responds to initial treatment and specifically, to their first two courses of drug treatment," said study author Patrick Kwan, MD, PhD, with the University of Melbourne in Australia.

For the study, 1,098 people from Scotland between the ages of nine and 93 with newly diagnosed epilepsy were followed for as long as 26 years after being given their first drug therapy. Participants were considered seizure-free if they had no seizures for at least a year without changes in their treatment. If they had further seizures, a second drug was chosen to be given alone or to be added to the first. If seizures continued, a third drug regimen was selected, and the process continued for up to nine drug regimens.

The study found that 50 percent of the people were seizure-free after the first drug tried, 13 percent were seizure-free after the second drug regimen tried and 4 percent were seizure-free after the third drug regimen tried. Less than two percent of the participants stopped having seizures on additional drug treatment courses up to the seventh one tried, and none became seizure-free after that.

The research also found that 37 percent of people in the study became seizure-free within six months of treatment. Another 22 percent became seizure-free after more than six months of starting treatment. Both groups continued to be seizure-free. However, 16 percent had fluctuating periods of seizure freedom and relapses, and 25 percent were never seizure-free for one year.

At the end of the study, 749 people (68 percent) were seizure-free and 678 people (62 percent) were on only one drug. The results were independent of the age when the person had the first seizure or the type of epilepsy.

"A person who doesn’t respond well to two courses of epilepsy drug treatment should be further evaluated to verify an epilepsy diagnosis and to identify whether surgery is the best next step," said Patricia E. Penovich, MD, with the Minnesota Epilepsy Group PA and the University of Minnesota School of Medicine in St. Paul, Minn., and a Fellow with the American Academy of Neurology, who wrote an accompanying editorial on the study.

Provided by American Academy of Neurology

Source: medicalxpress.com

May 9, 2012

In 1619, the pioneering astronomer Johannes Kepler published Harmonices Mundi in which he analyzed data on the movement of planets and asserted that the laws of nature governing the movements of planets show features of harmonic relationships in music. In so doing, Kepler provided important support for the, then controversial, model of the universe proposed by Copernicus.

In the latest issue of Biological Psychiatry, researchers at the University of California in San Diego suggest that careful analyses of the electrical signals of brain activity, measured using electroencephalography (EEG), may reveal important harmonic relationships in the electrical activity of brain circuits.

The underlying premise is a simple one - that brain function is expressed by circuits that fire, and therefore generate oscillating EEG signals, at different frequencies.

High frequency EEG activity called gamma, for example, might reflect the activity of fast-spiking cells which are often a subclass of inhibitory nerve cells containing parvalbumin. Represented musically, this would be a high pitch, i.e., toward the right side of the piano.

Lower frequency EEG activity, called theta, might come from cells that fire with a lower frequency.

As circuits interact with each other, one would see different “musical combinations”, like the chords of music, emerging in the EEG signal. Abnormalities in the structure and function of brain circuits would be reflected in cacophonous music, chords where the musical “voices” are firing at the wrong rate (pitch), volume (amplitude), or timing.

It is increasingly evident that schizophrenia is a disorder characterized by disturbances in the “music of the brain hemispheres.” This new report describes relationships between low- and high-frequency EEG oscillations in the human brain produced when high frequency auditory stimuli are presented to a research subject. The authors observed relatively slower oscillations and reduced cross-phase synchrony (for example, peak of theta coinciding with peak of gamma) in schizophrenia patients compared to healthy study participants.

Dr. John Krystal, Editor of Biological Psychiatry, commented, “The new findings highlight the importance of understanding the relationships between different circuits. It seems that cortical abnormalities in schizophrenia disturb brain function, in part, by disturbing the ‘tuning’ of brain circuits in relation to each other.”

Provided by Elsevier

Source: medicalxpress.com

May 9th, 2012

This family comprises a cluster of six genes that may be altered in neurological conditions, such as Parkinson’s and Charcot-Marie-Tooth disease.

A team headed by Eduardo Soriano at the Institute for Research in Biomedicine (IRB Barcelona) has published a study in Nature Communications describing a new family of six genes whose function regulates the movement and position of mitochondria in neurons. Many neurological conditions, including Parkinson’s and various types of Charcot-Marie-Tooth disease, are caused by alterations of genes that control mitochondrial transport, a process that provides the energy required for cell function.

“We have identified a set of new genes that are highly expressed in the nervous system and have a specific function in a biological process that is crucial for the activity and viability of the nervous system”, explains Eduardo Soriano, head of the Neurobiology and Cell Regeneration group at IRB Barcelona and full professor at the University of Barcelona (UB).

By means of comparative genomic analyses, the scientists have discovered that these genes are found only in more evolved mammals, the so-called Eutharia, these characterized by internal fertilization and development. “This finding indicates the relevance of mitochondrial biology. When the brain evolved in size, function and structure, the mitochondrial transport process also became more complex and probably required additional regulatory mechanisms”, says Soriano. “Likewise, given the origin of the gene cluster, in the transition between primitive mammals, such as marsupials (kangaroos) and the remaining placental mammals, it is tempting to propose that the cluster is linked to the increased complexity of the cerebral cortex in the lineage that leads to humans”, adds the full UB professor Jordi Garcia-Fernàndez, collaborator in the study.

In the image, red indicates the localization of mitochondria in a neuron. The new proteins described help to regulate their positions in the cell. Image adapted from IRB Barcelona press release image.

Correct brain function is highly energy-demanding. However, this energy must be finely distributed throughout neurons —cells that have ramifications that can reach up to tens of centimetres in length, from the brain to the limbs. This cluster of genes forms part of the “wheel” machinery of mitochondria and regulates the localization of each cell on the basis of its energy requirements. “These genes would be like an extra control in cellular mitochondrial trafficking and they interact with the major proteins associated with the regulation of mitochondrial transport”, explains Soriano.

Another striking characteristic of these new proteins is that they are found both in mitochondria, the function of which has already been described, and in the cell nucleus, where their function is unknown. “They may also be involved in the regulation of gene expression, a possibility that we are now studying”. In addition to their potential involvement in brain pathologies, the researchers believe that these proteins may be related to metabolic diseases and cancer.

Source: Neuroscience News