Posts tagged brain development
Articles and news from the latest research reports.
Brain development differs in children who stutter
UAlberta researcher and ISTAR executive director says study results could increase understanding of brain and speech production, improving treatment.
A new study by a University of Alberta researcher shows that children who stutter have less grey matter in key regions of the brain responsible for speech production than children who do not stutter.
The findings not only improve our understanding of how the brain is built for speech production and why people stutter, but also affirm the importance of seeking treatment early, using approaches such as those pioneered by the Institute for Stuttering Treatment and Research in the Faculty of Rehabilitation Medicine at the U of A, said Deryk Beal, ISTAR’s executive director.
Previous research has used MRI scans to look at structural differences between the brains of adults who stutter and those who do not. The problem with that approach is the scans come years after the onset of stuttering, typically between the ages of two and five years, Beal said.
“You can never be quite sure whether the differences in brain structure or function you’re looking at were the result of a lifetime of coping with a speech disorder or whether those brain differences were there from the beginning,” explained Beal, a speech-language pathologist.
For his study, Beal scanned the brains of 28 children ranging from five to 12 years old. Half the children were diagnosed with stuttering; the other half served as a control.
Results showed that the inferior frontal gyrus region of the brain develops abnormally in children who stutter. This is important because that part of the brain is thought to control articulatory coding—taking information our brain understands about language and sounds and coding it into speech movements.
“If you think about the characteristics of stuttering—repetitions of the first sounds or syllables in a word, prolongation of sounds in a word—it’s easy to hypothesize that it’s a speech-motor-control problem,” explained Beal. “The type of stuttering treatment we deliver at ISTAR is delivered with this limitation of the speech system in mind, and we have good success in stuttering treatment.”
Beal initiated the research at the University of Toronto and completed the work upon his arrival at the U of A. He sees the results as a first step toward testing to see how grey matter volumes are influenced by stuttering treatment and understanding motor-sequence learning differences between children who stutter and those who do not.
“The more we know about motor learning in these kids, the more we can adjust our treatment—deliver it in a shorter period of time, deliver it more effectively.”
The study was published in the September issue of the peer-reviewed journal Cortex and received funding from the Canadian Institutes of Health Research Clinical Fellowship and the Hospital for Sick Children’s Clinician Scientist Training Program.
How Infections in Newborns are Linked to Later Behavior Problems
In animal study, inflammation stops cells from accessing iron needed for brain development
Researchers exploring the link between newborn infections and later behavior and movement problems have found that inflammation in the brain keeps cells from accessing iron that they need to perform a critical role in brain development.
Specific cells in the brain need iron to produce the white matter that ensures efficient communication among cells in the central nervous system. White matter refers to white-colored bundles of myelin, a protective coating on the axons that project from the main body of a brain cell.
The scientists induced a mild E. coli infection in 3-day-old mice. This caused a transient inflammatory response in their brains that was resolved within 72 hours. This brain inflammation, though fleeting, interfered with storage and release of iron, temporarily resulting in reduced iron availability in the brain. When the iron was needed most, it was unavailable, researchers say.
“What’s important is that the timing of the inflammation during brain development switches the brain’s gears from development to trying to deal with inflammation,” said Jonathan Godbout, associate professor of neuroscience at The Ohio State University and senior author of the study. “The consequence of that is this abnormal iron storage by neurons that limits access of iron to the rest of the brain.”
The research is published in the Oct. 9, 2013, issue of The Journal of Neuroscience.
The cells that need iron during this critical period of development are called oligodendrocytes, which produce myelin and wrap it around axons. In the current study, neonatal infection caused neurons to increase their storage of iron, which deprived iron from oligodendrocytes.
In other mice, the scientists confirmed that neonatal E. coli infection was associated with motor coordination problems and hyperactivity two months later – the equivalent to young adulthood in humans. The brains of these same mice contained lower levels of myelin and fewer oligodendrocytes, suggesting that brief reductions in brain-iron availability during early development have long-lasting effects on brain myelination.
The timing of infection in newborn mice generally coincides with the late stages of the third trimester of pregnancy in humans. The myelination process begins during fetal development and continues after birth.
Though other researchers have observed links between newborn infections and effects on myelin and behavior, scientists had not figured out why those associations exist. Godbout’s group focuses on understanding how immune system activation can trigger unexpected interactions between the central nervous system and other parts of the body.
“We’re not the first to show early inflammatory events can change the brain and behavior, but we’re the first to propose a detailed mechanism connecting neonatal inflammation to physiological changes in the central nervous system,” said Daniel McKim, a lead author on the paper and a student in Ohio State’s Neuroscience Graduate Studies Program.
The neonatal infection caused several changes in brain physiology. For example, infected mice had increased inflammatory markers, altered neuronal iron storage, and reduced oligodendrocytes and myelin in their brains. Importantly, the impairments in brain myelination corresponded with behavioral and motor impairments two months after infection.
Though it’s unknown if these movement problems would last a lifetime, McKim noted that “since these impairments lasted into what would be young adulthood in humans, it seems likely to be relatively permanent.”
The reduced myelination linked to movement and behavior issues in this study has also been associated with schizophrenia and autism spectrum disorders in previous work by other scientists, said Godbout, also an investigator in Ohio State’s Institute for Behavioral Medicine Research (IBMR).
“More research in this area could confirm that human behavioral complications can arise from inflammation changing the myelin pattern. Schizophrenia and autism disorders are part of that,” he said.
This current study did not identify potential interventions to prevent these effects of early-life infection. Godbout and colleagues theorize that maternal nutrition – a diet high in antioxidants, for example – might help lower the inflammation in the brain that follows a neonatal infection.
“The prenatal and neonatal period is such an active time of development,” Godbout said. “That’s really the key – these inflammatory challenges during critical points in development seem to have profound effects. We might just want to think more about that clinically.”
What evolved first - a dexterous hand or an agile foot?
Resolving a long-standing mystery in human evolution, new research from the RIKEN Brain Science Institute indicates that early hominids developed finger dexterity and tool use ability before the development of bipedal locomotion.
Combining monkey and human behavior, brain imaging, and fossil evidence, a research team led by neurobiologist Dr. Atsushi Iriki and including Dr. Gen Suwa, an anthropologist from the University of Tokyo Museum, have overturned the common assumption that manual dexterity evolved after the development of bipedal locomotion freed hominid hands to use fingers for tool manipulation.
In a study published today in Philosophical Transactions of the Royal Society B, the researchers employed functional magnetic resonance imaging in humans and electrical recording from monkeys to locate the brain areas responsible for touch awareness in individual fingers and toes, called somatotopic maps. With these maps, the researchers confirmed previous studies showing that single digits in the hand and foot have discrete neural locations in both humans and monkeys.
However, the researchers found new evidence that monkey toes are combined into a single map, while human toes are also fused into a single map, but with the prominent exception of the big toe, which has its own map not seen in monkeys. These findings suggest that early hominids evolved dexterous fingers when they were still quadrupeds. Manual dexterity was not further expanded in monkeys, but humans gained fine finger control and a big toe to aid bipedal locomotion.
“In early quadruped hominids, finger control and tool use were feasible, while an independent adaptation involving the use of the big toe for functions like balance and walking occurred with bipedality,” the authors explained.
The brain study was supported by analysis of the well-preserved hand and feet bones of a 4.4 million year-old skeleton of the quadruped hominid Ardipithecus ramidus, a species with hand dexterity that preceded the human-monkey lineage split.
The findings suggest that the parallel evolution of two-legged locomotion and manual dexterity in hands and fingers in the human lineage were a consequence of adaptive pressures on ancestral quadrupeds for balance control by foot digits while retaining the critical capability for fine finger specialization.
“Evolution is not usually thought of as being accessible to study in the laboratory”, stated Dr. Iriki, “but our new method of using comparative brain physiology to decipher ancestral traces of adaptation may allow us to re-examine Darwin’s theories”.
Babies learn to anticipate touch in the womb
Babies learn how to anticipate touch while in the womb, according to new research.
Using 4-d scans psychologists at Durham and Lancaster universities found, for the first time, that fetuses were able to predict, rather than react to, their own hand movements towards their mouths as they entered the later stages of gestation compared to earlier in a pregnancy.
The Durham-led team of researchers said that the latest findings could improve understanding about babies, especially those born prematurely, their readiness to interact socially and their ability to calm themselves by sucking on their thumb or fingers.
They said the results could also be a potential indicator of how prepared babies are for feeding.
The researchers carried out a total of 60 scans of 15 healthy fetuses at monthly intervals between 24 weeks and 36 weeks gestation.
Fetuses in the earlier stage of gestation more frequently touched the upper part and sides of their heads.
As the fetuses matured they began to increasingly touch the lower, more sensitive, part of their faces including their mouths.
By 36 weeks a significantly higher proportion of fetuses were observed opening their mouths before touching them, suggesting that later in pregnancy they were able to anticipate that their hands were about to touch their mouths, rather than reacting to the touch of their hands, the researchers said.
Increased sensitivity around a fetus’ mouth at this later stage of pregnancy could mean that they have more “awareness” of mouth movement, they added.
Previous theories have suggested that movement in sequence could form the basis for the development of intention in fetuses.
The researchers said their findings could potentially be an indicator of healthy development, as arguably fetuses who are delayed in this development due to illness, such as growth restriction, might not show the same behaviour observed during the study.
The research, published in the journal Developmental Psychobiology, involved eight girls and seven boys and the researchers noticed no difference in behaviour between boys and girls.
Lead author Dr Nadja Reissland, in the Department of Psychology, at Durham University, said: “Increased touching of the lower part of the face and mouth in fetuses could be an indicator of brain development necessary for healthy development, including preparedness for social interaction, self-soothing and feeding.
“What we have observed are sequential events, which show maturation in the development of fetuses, which is the basis for life after birth.
“The findings could provide more information about when babies are ready to engage with their environment, especially if born prematurely.”
Brian Francis, Professor of Social Statistics at Lancaster, added: “This effect is likely to be evolutionally determined, preparing the child for life outside the womb. Building on these findings, future research could lead to more understanding about how the child is prepared prenatally for life, including their ability to engage with their social environment, regulate stimulation and being ready to take a breast or bottle.”
The study builds on previous research by Durham and Lancaster into fetal development. Earlier this year another of their studies showed that unborn babies practise facial expressions in the womb in what is thought to be preparation for communicating after birth.
And in 2012 Dr Reissland published research showing that unborn babies yawn in the womb, suggesting that yawning is a developmental process which could potentially give doctors another index of a fetus’ health.
Researchers find how viral infection disrupts neural development in offspring, increasing risk of autism
Activating a mother’s immune system during her pregnancy disrupts the development of neural cells in the brain of her offspring and damages the cells’ ability to transmit signals and communicate with one another, researchers with the UC Davis Center for Neuroscience and Department of Neurology have found. They said the finding suggests how maternal viral infection might increase the risk of having a child with autism spectrum disorder or schizophrenia.
The research, “MHCI Requires MEF2 Transcription Factors to Negatively Regulate Synapse Density during Development and in Disease,” is published in the Journal of Neuroscience.
The study’s senior author is Kimberley McAllister, professor in the Center for Neuroscience with appointments in the departments of Neurology and Neurobiology, Physiology and Behavior, and a researcher with the UC Davis MIND Institute.
“This is the first evidence that neurons in the developing brain of newborn offspring are altered by maternal immune activation,” McAllister said. “Until now, very little has been known about how maternal immune activation leads to autism spectrum disorder and schizophrenia-like pathophysiology and behaviors in the offspring.”
The study was conducted in mice and rats and compared the brains of the offspring of rodents whose immune systems had been activated and those of animals whose immune systems had not been activated. The pups of animals that were exposed to viral infection had much higher brain levels of immune molecules known as the major histocompatibility complex I (MHCI) molecules.
“This is the first evidence that MHCI levels on the surface of young cortical neurons in offspring are altered by maternal immune activation,” McAllister said.
The researchers found that the high MHCI levels impaired the ability of the neurons from the newborn mice’s brains to form synapses, the tiny gaps separating brain cells through which signals are transmitted. Earlier research has suggested that ASD and schizophrenia may be caused by changes in the development of connections in the brain, especially the cerebral cortex.
The researchers experimentally reduced MHCI to normal levels in neurons from offspring following maternal immune activation.
“Remarkably, synapse density returned to normal levels in those neurons,” McAllister said.
“These results indicate that maternal immune activation does indeed alter connectivity during prenatal development, causing a profound deficit in the ability of cortical neurons to form synapses that is caused by changes in levels of MHCI on the neurons,” she said.
MHCI did not work alone to limit the development of synapses. In a series of experiments, the UC Davis researchers determined that MHCI interacted with calcineurin and myocyte enhancer factor-2 (Mef2), a protein that is a critical determinant of neuronal specialization.
MHCI, calcineurin and Mef2 form a biological signaling pathway that had not been previously identified. McAllister’s team showed that in the offspring of the maternal immune activation mothers, this novel signaling pathway was much more active than it was in the offspring of non-MIA animals.
“This finding provides a potential mechanism linking maternal immune activation to disease-linked behaviors,” McAllister said.
It also is a mechanism that may help McAllister and other scientists to develop diagnostic tests and eventually therapies to improve the lives of individuals with these neurodevelopmental disorders.
(Source: ucdmc.ucdavis.edu)
During pregnancy, the bone hormone osteocalcin is produced by the mother; it crosses the placenta, to reach the fetus, where it promotes the formation of the hippocampus and the development of spatial learning and memory. Postnatally, osteocalcin crosses the blood-brain barrier (BBB), to act in various regions of the brain, including the hippocampus, where it causes changes in brain chemistry that help prevent anxiety and depression and improve spatial learning and memory.
Image credit: Gerard Karsenty, MD, PhD and Franck Oury, PhD/Columbia University Medical Center
Bone Hormone Influences Brain Development and Cognition
Findings could lead to new treatments for memory loss, anxiety, and depression
Researchers from Columbia University Medical Center (CUMC) have found that the skeleton, acting through the bone-derived hormone osteocalcin, exerts a powerful influence on prenatal brain development and cognitive functions such as learning, memory, anxiety, and depression in adult mice. Findings from the mouse study could lead to new approaches to the prevention and treatment of neurologic disorders. The study was published today in the online edition of Cell.
“The brain is commonly viewed as an organ that influences other organs and parts of the body, but less often as the recipient of signals coming from elsewhere, least of all, the bones,” said study leader Gerard Karsenty, MD, PhD, Paul A. Marks Professor of Genetics and Development, professor of medicine, and chair of the Department of Genetics and Development.
“In an earlier study, we showed that the brain is a powerful inhibitor of bone mass accrual,” he said. “This effect was so powerful that it immediately raised the question, ‘Does the bone signal back to the brain to limit this negative influence?’ ‘If so, what signals does it use and how do they work?’”
Dr. Karsenty suspected that osteocalcin, a hormone recently identified by his lab and secreted by osteoblasts, might be involved in such bone-to-brain signaling. Earlier studies had shown that osteocalcin affects a variety of processes, such as energy expenditure, glucose balance, and male fertility. “Since most hormones influence a range of physiological processes, it was reasonable to assume that the endocrine functions of osteocalcin were even broader than what was already known,” he said.
To determine whether osteocalcin did indeed play a role in the brain, Dr. Karsenty and his team studied “osteocalcin-null” mice (mice that have been genetically engineered to not produce any osteocalcin). Using these mice, they were able to show unambiguously that osteocalcin can cross the blood-brain barrier; binds to neurons in the brainstem, midbrain, and hippocampus (which is responsible for learning and memory); promotes the birth of neurons; and increases the synthesis of several neurotransmitters, including serotonin, dopamine, and catecholamine. They also found that osteocalcin-null mice had abnormally small hippocampi, a part of the brain involved in memory.
The researchers then hypothesized that the changes in neurotransmitter synthesis should alter the animals’ behavior. In a series of behavioral tests, they confirmed that osteocalcin-null mice exhibit increased anxiety and depression-like behaviors, as well as impaired learning and memory, compared with normal mice.
These changes are similar to those seen in the aging population. “As we age, bone mass decreases, and the production of osteocalcin probably does, too,” said Dr. Karsenty. “We’re currently looking into this. It is not inconceivable that treatments that boost osteocalcin levels or stimulate osteocalcin receptors could help counter the cognitive effects of aging and aging-related diseases such as Alzheimer’s.”
When adult osteocalcin-null mice were infused with osteocalcin, their anxiety and depression did decrease, “but the infusions didn’t affect learning and memory or the size of the hippocampus,” said Dr. Karsenty. “This was perplexing, so we did another experiment—a postnatal knockout of osteocalcin (a genetically engineered model in which the synthesis of osteocalcin is blocked after birth). These mice were anxious and depressed but had normal memory and hippocampus structure. The unavoidable conclusion of the two experiments was that osteocalcin must act during development.” This led to the second part of their study.
In subsequent experiments, the researchers showed that osteocalcin crosses the placenta from mother to fetus and that this maternal pool of osteocalcin is necessary for formation of the hippocampus and the establishment of memory. Lastly, they showed that once-a-day injections of osteocalcin in osteocalcin-null mothers during pregnancy could prevent the development of behavioral abnormalities in their offspring.
“This finding could explain some of the effects observed in children born from undernourished mothers who develop, with an unusually high frequency, metabolic and psychiatric disorders just as osteocalcin-null mice do,” said Dr. Karsenty. “Malnutrition decreases the activity of bone cells; as a result, undernourished mothers have low bone mass, which affects osteocalcin production. This has clinical relevance even today, in developing countries, where maternal malnutrition is still common.”
Any therapies related to osteocalcin are still years away, however, he added.
Caffeine consumption slows down brain development
Humans and other mammals show particularly intensive sleeping patterns during puberty. The brain also matures fastest in this period. But when pubescent rats are administered caffeine, the maturing processes in their brains are delayed. This is the result of a study supported by the Swiss National Science Foundation (SNSF).
Children’s and young adults’ average caffeine consumption has increased by more than 70 per cent over the past 30 years, and an end to this rise is not in sight: the drinks industry is posting its fastest-growing sales in the segment of caffeine-laden energy drinks. Not everybody is pleased about this development. Some people are worried about possible health risks caused in young consumers by the pick-me-up.
Researchers led by Reto Huber of the University Children’s Hospital Zurich are now adding new arguments to the debate. In their recently published study conducted on rats, the conclusions call for caution: in pubescent rodents, caffeine intake equating to three to four cups of coffee per day in humans results in reduced deep sleep and a delayed brain development.
Peak level during puberty
Both in humans and in rats, the duration and intensity of deep sleep as well as the number of synapses or connections in the brain increase during childhood, reaching their highest level during puberty and dropping again in adult age. “The brain of children is extremely plastic due to the many connections,” says Huber. When the brain then begins to mature during puberty, a large number of these connections are lost. “This optimisation presumably occurs during deep sleep. Key synapses extend, others are reduced; this makes the network more efficient and the brain more powerful,” says Huber.
Timid instead of curious
Huber’s group of researchers administered moderate quantities of caffeine to 30-day-old rats over five days and measured the electrical current generated by their brains. The deep sleep periods, which are characterised by slow waves, were reduced from day 31 until day 42, i.e. well beyond the end of administering caffeine. Compared to the rats being given pure drinking water, the researchers found far more neural connections in the brains of the caffeine-drinking animals at the end of the study. The slower maturing process in the brain also had an impact on behaviour: rats normally become more curious with age, but the rats consuming caffeine remained timid and cautious.
The brain goes through a delicate maturing phase in puberty, during which many mental diseases can break out. And even if the rat brain differs clearly from that of humans, the many parallels in how the brains develop raise the question as to whether children’s and young adults’ caffeine intake really is harmless or whether it might be wiser to abstain from consuming the pick-me-up. “There is still need for research in this area,” says Huber.
(Source: snf.ch)
Building the best brain: U-M researchers show how brain cell connections get cemented early in life
Research on synapse stabilization could aid understanding of autism, schizophrenia, intellectual disability
When we’re born, our brains aren’t very organized. Every brain cell talks to lots of other nearby cells, sending and receiving signals across connections called synapses.
But as we grow and learn, things get a bit more stable. The brain pathways that will serve us our whole lives start to organize, and less-active, inefficient synapses shut down.
But why and how does this happen? And what happens when it doesn’t go normally? New research from the University of Michigan Medical School may help explain.
In a new paper in Nature Neuroscience, a team of U-M neuroscientists reports important findings about how brain cells called neurons keep their most active connections with other cells, while letting other synapses lapse.
Specifically, they show that SIRP alpha, a protein found on the surface of various cells throughout the body, appears to play a key role in the process of cementing the most active synaptic connections between brain cells. The research, done in mouse brains, was funded by the National Institutes of Health and several foundations.
The findings boost understanding of basic brain development – and may aid research on conditions like autism, schizophrenia, epilepsy and intellectual disability, all of which have some basis in abnormal synapse function.
“For the brain to be really functional, we need to keep the most active and most efficient connections,” says senior author Hisashi Umemori, M.D., Ph.D., a research assistant professor at U-M’s Molecular and Behavioral Neuroscience Institute and assistant professor of biological chemistry in the Medical School. “So, during development it’s crucial to establish efficient connections, and to eliminate inactive ones. We have identified a key molecular mechanism that the brain uses to stabilize and maturate the most active connections.”
Umemori says the new findings on SIRP alpha grew directly out of previous work on competition between neurons, which enables the most active ones to become part of pathways and circuits. (Read more on this research)
The team suspected that there must be some sort of signal between the two cells on either side of each synapse — something that causes the most active synapses to stabilize. So they set out to find out what it was.
SIRP-rise findings
The group had previously shown that SIRP-alpha was involved in some way in a neuron’s ability to form a presynaptic nerve terminal – an extension of the cell that reaches out toward a neighboring cell, and can send the chemical signals that brain cells use to talk to one another.
SIRP-alpha is also already known to serve an important function in the rest of the body – essentially, helping normal cells tell the immune system not to attack them. It may also help cancer cells evade detection by the immune system’s watchdogs.
In the new study, the team studied SIRP alpha function in the brain – and started to understand its role in synapse stabilization. They focused on the hippocampus, a region of the brain very important to learning and memory.
Through a range of experiments, they showed that when a brain cell receives signals from a neighboring cell across a synapse, it actually releases SIRP-alpha into the space between the cells. It does this through the action of molecules inside the cell – called CaMK and MMP – that act like molecular scissors, cutting a SIRP-alpha protein in half so that it can float freely away from the cell.
The part of the SIRP-alpha protein that floats into the synapse “gap” latches on to a receptor on the other side, called a CD47 receptor. This binding, in turn, appears to tell the cell that the signal it sent earlier was indeed received – and that the synapse is a good one. So, the cell brings more chemical signaling molecules down that way, and releases them into the synapse.
As more and more nerve messages travel between the “sending” and “receiving” cells on either side of that synapse, more SIRP-alpha gets cleaved, released into the synapse, and bound to CD47.
The researchers believe this repeated process is what helps the cells determine which synapses to keep – and which to let wither.
Umemori says the team next wants to look at what happens when SIRP-alpha doesn’t get cleaved as it should – and at what’s happening in cells when a synapse gets eliminated.
“This step of shedding SIRP-alpha must be critical to developing a functional neural network,” he says. “And if it’s not done well, disease or disorders may result. Perhaps we can use this knowledge to treat diseases caused by defects in synapse formation.”
He notes that the gene for the CD47 receptor is found in the same general area of our DNA as several genes that are suspected to be involved in schizophrenia.
Worm research: Right combination of sugars regulates brain development
If the development of our nervous system is disturbed, we risk developing serious neurological diseases, impairing our sensory systems, movement control or cognitive functions. This is true for all organisms with a well-developed nervous system, from man to worm. New research from BRIC, University of Copenhagen reveals how a tiny molecule called mir-79 regulates neural development in roundworms. The molecule is required for correct migration of specific nerve cells during development and malfunction causes defects in the nervous system of the worm. The research has just been published in the journal Science.
Hundreds of worms lie in a small plastic plate under the laboratory microscope. Over the last three years, the group of Associate Professor Roger Pocock has used the roundworm C. elegans tostudy the development of the nervous system. They have just made an important discovery.
“Our new results show that a small molecule called mir-79 is indispensable for development of the worm’s nervous system. mir-79 acts by equipping special signal molecules with a transmitter, which tells the nerve cells how they should migrate during development of the worm. If we remove mir-79 with gene technology, development of the worm nervous system goes awry”, says postdoc Mikael Egebjerg Pedersen, who is responsible for the experimental studies.
mir-79 adds just the right combination of sugar
The research shows that mir-79 acts by controlling the addition of certain groups of sugars to selected signaling molecules. In the world of cells, sugar molecules act as transmitters.
When the nerve cells come into contact with the sugar-transmitters, they are informed where to locate themselves during neural development. If the researchers remove mir-79, the migration of the nerve cells is misguided causing neuronal defects in the worms.
“It has earlier been shown that signaling molecules guide nerve migration, but our research shows that mir-79 regulates nerve cell migration by controlling the correct balance of sugar-transmitters on signaling molecules. If mir-79 does not function, the worm nervous system is malformed. In the wild, such defects would be harmful for worm survival”, explains Roger Pocock who leads the research group behind the finding.
Worm studies reveal important clues for neuronal repair
A version of mir-79 called mir-9 is found in humans. Therefore, these results are important for understanding how our nervous system develops during fetal development. In addition, the results add to the understanding of how nerve cells may be stimulated to repair damage in our brain or spinal cord.
“Our nervous system is a tissue which is not easily repaired after damage. So, how certain molecular cues can stimulate nerve cells to migrate is an important brick in the puzzle. This will enable us to understand how nerve tissue can be regenerated after, for example, a stroke or an accident. If we can use such knowledge to mimic the signals, we may be able to stimulate nerve cells to migrate into a damaged area”, says Roger Pocock.
Worms are a fantastic model to study how the nervous system develops and how nerve cells form neuronal circuits. Most of the genes that control nervous system development in the worm are also found in humans. At the same time, the reduced complexity of the worm nervous system allows researchers to investigate central biological mechanisms. With new technologies they can mark single cells or molecules, and as worms are transparent, the researchers can track the marked molecules or cells live during worm development.
The next step for the researchers is to investigate how the regulatory pathway they have revealed is regulated in cultures of human cells.
(Source: news.ku.dk)
Researchers Find Surprising Role of Critical Brain Protein
If the violins were taken away from the musicians performing Beethoven’s 9th symphony, the resulting composition would sound very different. If the violins were left on stage but the violinists were removed, the same mutant version of the symphony would be heard.
But what if it ended up sounding like “Hey Jude” instead?
This sort of surprise is what scientists from the Virginia Tech Carilion Research Institute had during what they assumed to be a routine experiment in neurodevelopment. Previous studies had shown that the glycoprotein Reelin is crucial to developing healthy neural networks. Logically, taking away the two receptors that Reelin is known to act on early in the brain’s development should create the same malformations as taking away Reelin itself.
It didn’t.
“We conducted the experiment thinking we’d see the same defects for both cases – Reelin deficiency and its receptors’ deletion – but we didn’t,” said Michael Fox, an associate professor at the research institute and the lead author of the study. “If you take away the receptors instead of the targeting molecule, you get an entirely separate set of abnormalities. The results raise the question of the identity of other molecules with which Reelin and the two receptors are interacting.”
The study, first published online in June in Neural Development, could prove useful for the development of therapies and diagnostics to combat brain disease.
In the early stages of neural development, neurons grow from the retina to a small portion of the brain called the thalamus. All sensory information coming into the brain gets routed through this region, before being transmitted to the cerebral cortex for further processing. Because these retinal neurons carry specific types of information, they must connect to specific places in the thalamus, which Reelin helps them find.
In the experiment, the scientists bred mice lacking both Reelin receptors known to be critical for neurons to navigate their targets during development. The scientists expected the neurons in the mutants to become lost and unable to find their targets, which is what happens in Reelin-deficient mice. Instead, the neurons were able to locate their targets, but those targets had wandered off.
While these results were surprising, they weren’t the most interesting of the experiment. Although most neurons look the same to people without advanced training in neuroscience, many different types are intermixed in distinct regions with strict borders. How these borders are formed, however, is still an open question.
“Many of us have questioned how you can have such a crisp boundary between two regions of the brain,” said Jianmin Su, a research assistant professor at the research institute and first author of the study. “I always thought it was a large number of cells creating some kind of cue or environment, but that isn’t what this experiment indicates.”
In the mice without the Reelin receptors, neurons from one part of the thalamus migrated to an area where they weren’t supposed to be. Even though only a handful of neurons were misplaced, they did not mingle with their new neighbors. They stayed separate.
“The result is a baffling curiosity that nobody in the lab expected – just how distinct these little regions can be,” Fox said. “How do just a few cells create such a barrier? How many cells does it take? Maybe these little islands can teach us something about how you create boundaries between larger regions of functionally similar cells.”
This experiment isn’t the only example Fox has had recently of neurons invading regions in which they weren’t supposed to be. In a second experiment, researchers examined how neurons from the cortex connect to the thalamus during the initial stages of development.
And neurons seem to be polite.
The results showed that neurons from the cortex grow to the edge of the part of the thalamus dedicated to visual signals, called the dorsal lateral geniculate nucleus, but then stop. In fact, they stay on standby for nearly two weeks before making their way into the region. It seems as though they’re waiting for the retinal neurons to make their connections before beginning to make their own. If researchers surgically removed the eyes or genetically removed the retinal cells connecting the eyes to the thalamus, neurons from the cortex invaded more than a week earlier than they were supposed to.
“It turns out that the cortical neurons are waiting for the retinal axons to mature and find the most appropriate spots to connect before they’re allowed to come in,” said Fox. “There’s some form of instructional role that retinal axons play in the timing of the cortical axons entering.”
(Source: newswise.com)