Posts tagged nervous system
Articles and news from the latest research reports.
How Rabies “Hijacks” Neurons to Attack the Brain
Rabies causes acute inflammation of the brain, producing psychosis and violent aggression. The virus, which paralyzes the body’s internal organs, is always deadly for those unable to obtain vaccines in time. Some 55,000 people die from rabies every year.
For the first time, Tel Aviv University scientists have discovered the exact mechanism this killer virus uses to efficiently enter the central nervous system, where it erupts in a toxic explosion of symptoms. The study, published in PLOS Pathogens, was conducted by Dr. Eran Perlson and Shani Gluska of TAU’s Sackler Faculty of Medicine and Sagol School of Neuroscience, in collaboration with the Friedrich Loeffler Institute in Germany.
"Rabies not only hijacks the nervous system’s machinery, it also manipulates that machinery to move faster," said Dr. Perlson. "We have shown that rabies enters a neuron in the peripheral nervous system by binding to a nerve growth factor receptor, responsible for the health of neurons, called p75. The difference is that its transport is very fast, even faster than that of its endogenous ligand, the small molecules that travel regularly along the neuron and keep the neuron healthy."
Faster than a speeding train
To track the rabies virus in the nervous system, the researchers grew mouse sensory neurons in an observation chamber and used live cell imaging to track the path taken by the virus particles. The researchers “saw” the virus hijack the “train” transporting cell components along a neuron and drove it straight into the spinal cord. Once in the spinal cord, the virus caught the first available train to the brain, where it wrought havoc before speeding through the rest of the body, shutting it down organ by organ.
Nerve cells, or neurons, outside the central nervous system are highly asymmetric. A long protrusion called an axon extends from the cell body to another nerve cell or organ along a specific transmission route. In addition to rapid transmission of electric impulses, axons also transport molecular materials over these distances.
"Axonal transport is a delicate and crucial process for neuronal survival, and when disrupted it can lead to neurodegenerative diseases," said Dr. Perlson. "Understanding how an organism such as rabies manipulates this machinery may help us in the future to either restore the process or even to manipulate it to our own therapeutic needs."
Hijacking the hijacker
"A tempting premise is to use this same machinery to introduce drugs or genes into the nervous system," Dr. Perlson added. By shedding light on how the virus hijacks the transport system in nerve cells to reach its target organ with maximal speed and efficiency, the researchers hope their findings will allow scientists to control the neuronal transport machinery to treat rabies and other neurodegenerative diseases.
Disruptions of the neuron train system also contribute to neurodegenerative diseases, like Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). According to Dr. Perlson, “An improved understanding of how the neuron train works could lead to new treatments for these disorders as well.”
Do Gut Bacteria Rule Our Minds?
It sounds like science fiction, but it seems that bacteria within us — which outnumber our own cells about 100-fold — may very well be affecting both our cravings and moods to get us to eat what they want, and often are driving us toward obesity.
In an article published this week in the journal BioEssays, researchers from UC San Francisco, Arizona State University and University of New Mexico concluded from a review of the recent scientific literature that microbes influence human eating behavior and dietary choices to favor consumption of the particular nutrients they grow best on, rather than simply passively living off whatever nutrients we choose to send their way.
Bacterial species vary in the nutrients they need. Some prefer fat, and others sugar, for instance. But they not only vie with each other for food and to retain a niche within their ecosystem — our digestive tracts — they also often have different aims than we do when it comes to our own actions, according to senior author Athena Aktipis, PhD, co-founder of the Center for Evolution and Cancer with the Helen Diller Family Comprehensive Cancer Center at UCSF.
While it is unclear exactly how this occurs, the authors believe this diverse community of microbes, collectively known as the gut microbiome, may influence our decisions by releasing signaling molecules into our gut. Because the gut is linked to the immune system, the endocrine system and the nervous system, those signals could influence our physiologic and behavioral responses.
“Bacteria within the gut are manipulative,” said Carlo Maley, PhD, director of the UCSF Center for Evolution and Cancer and corresponding author on the paper. “There is a diversity of interests represented in the microbiome, some aligned with our own dietary goals, and others not.”
Fortunately, it’s a two-way street. We can influence the compatibility of these microscopic, single-celled houseguests by deliberating altering what we ingest, Maley said, with measurable changes in the microbiome within 24 hours of diet change.
“Our diets have a huge impact on microbial populations in the gut,” Maley said. “It’s a whole ecosystem, and it’s evolving on the time scale of minutes.”
There are even specialized bacteria that digest seaweed, found in humans in Japan, where seaweed is popular in the diet.
Research suggests that gut bacteria may be affecting our eating decisions in part by acting through the vagus nerve, which connects 100 million nerve cells from the digestive tract to the base of the brain.
“Microbes have the capacity to manipulate behavior and mood through altering the neural signals in the vagus nerve, changing taste receptors, producing toxins to make us feel bad, and releasing chemical rewards to make us feel good,” said Aktipis, who is currently in the Arizona State University Department of Psychology.
In mice, certain strains of bacteria increase anxious behavior. In humans, one clinical trial found that drinking a probiotic containing Lactobacillus casei improved mood in those who were feeling the lowest.
Maley, Aktipis and first author Joe Alcock, MD, from the Department of Emergency Medicine at the University of New Mexico, proposed further research to test the sway microbes hold over us. For example, would transplantation into the gut of the bacteria requiring a nutrient from seaweed lead the human host to eat more seaweed?
The speed with which the microbiome can change may be encouraging to those who seek to improve health by altering microbial populations. This may be accomplished through food and supplement choices, by ingesting specific bacterial species in the form of probiotics, or by killing targeted species with antibiotics. Optimizing the balance of power among bacterial species in our gut might allow us to lead less obese and healthier lives, according to the authors.
“Because microbiota are easily manipulatable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating,” the authors wrote.
The authors met and first discussed the ideas in the BioEssays paper at a summer school conference on evolutionary medicine two years ago. Aktipis, who is an evolutionary biologist and a psychologist, was drawn to the opportunity to investigate the complex interaction of the different fitness interests of microbes and their hosts and how those play out in our daily lives. Maley, a computer scientist and evolutionary biologist, had established a career studying how tumor cells arise from normal cells and evolve over time through natural selection within the body as cancer progresses.
In fact, the evolution of tumors and of bacterial communities are linked, points out Aktipis, who said some of the bacteria that normally live within us cause stomach cancer and perhaps other cancers.
“Targeting the microbiome could open up possibilities for preventing a variety of disease from obesity and diabetes to cancers of the gastro-intestinal tract. We are only beginning to scratch the surface of the importance of the microbiome for human health,” she said.
Researchers Uncover an Unexpected Role for Endostatin in the Nervous System
Researchers at UC San Francisco have discovered that endostatin, a protein that once aroused intense interest as a possible cancer treatment, plays a key role in the stable functioning of the nervous system.
A substance that occurs naturally in the body, endostatin potently blocks the formation of new blood vessels. In studies in mice in the late 1990s, endostatin treatment virtually eliminated cancer by shutting down the blood supply to tumors, but subsequent human clinical trials proved disappointing.
“It was a very big surprise” to find that endostatin, through some other mechanism, helps to maintain the proper workings of synapses, the sites where communication between nerve cells takes place, said Graeme W. Davis, PhD, Hertzstein Distinguished Professor of Medicine in the Department of Biochemistry and Biophysics at UCSF and senior author of the new study. “Endostatin was not on our radar.”
The findings were reported online July 24 in the journal Neuron.
Synapses are continually shaped and reshaped by experience, a phenomenon known as plasticity. But for those changes to be meaningful, said Davis, they must take place against a stable background, which paradoxically requires another form of change that he and colleagues call “homeostatic plasticity.” Just as we change our pace, slowing down or speeding up, to keep abreast of a running partner, neurons adjust aspects of their function at synapses to compensate for changes in their synaptic partners brought on by aging, illness, or other factors.
In an example of homeostatic plasticity, in the neuromuscular disease myasthenia gravis, as muscle cells become less responsive to the neurotransmitter acetylcholine, nerve cells ramp up their secretion of the neurotransmitter to keep the system in balance for as long as possible. Some researchers believe that in other disorders, including autism and schizophrenia, a failure in such homeostatic mechanisms keeps synapses from functioning properly.
In previous research Davis noticed that applying a toxin to a muscle cell in the fruit fly Drosophila melanogaster triggers homeostatic plasticity in the neuron that forms a synapse on that muscle cell: the neuron—which is called presynaptic, because it is “before” the synapse with the muscle cell—reliably releases more neurotransmitter, just as happens when muscle cells begin to malfunction in myasthenia gravis.
Davis has since built on this model of homeostatic plasticity by painstakingly knocking out Drosophila genes one by one and recording from presynaptic neurons to see which genes are necessary for the homeostatic response, because it is these genes that may be compromised in diseases affecting the process.
“So far we’ve tested about 1,000 genes this way, which has entailed close to 10,000 recordings,” Davis said.
Using this technique Davis and colleagues observed at one point that knocking out a gene called multiplexin significantly hampered homeostatic plasticity in presynaptic neurons. But because that gene helps to form a structural protein known as collagen—which in humans is a component of ligaments, tendons, and cartilage—the finding wasn’t immediately considered relevant to synaptic function.
The team learned that the multiplexin protein can be snipped by an enzyme to produce endostatin, so in experiments led by postdoctoral fellow Tingting Wang, PhD, they tested whether endostatin might play a role in homeostatic plasticity.
“Nobody picked up multiplexin to work on for a couple of years, because we didn’t think a collagen could be that interesting,” Davis said. “Then, when a new postdoc, Tingting Wang, came to the lab, we started thinking about it harder.”
When the group genetically deleted the portion of Drosophila multiplexin that forms endostatin, presynaptic neurons behaved normally, but homeostatic plasticity was severely compromised when toxin was applied to postsynaptic muscle cells. On the opposite side of the coin, when the team overexpressed endostatin at Drosophila synapses lacking multiplexin, homeostasis was restored, whether endostatin was expressed in muscle cells or presynaptic neurons.
The research team is unsure precisely how and where endostatin exerts its effects on homeostatic plasticity, but they believe that multiplexin is cleaved at the postsynaptic site to form endostatin, and that the endostatin signal is conveyed to the presynaptic neuron to alter its function. “Because so many people in the cancer world have studied endostatin, there is a great set of tools available” to study the protein, Davis said, so he expects his group to make rapid progress in addressing these questions.
“Despite its checkered history in cancer, we know endostatin is a signaling molecule and we know that the brain has a great deal of collagen—we just haven’t known what it does, and we certainly don’t know what endostatin’s receptors in the brain might be.” Davis said. “But it’s pretty exciting to think about a new signaling molecule with a profound role in the stabilization of the function of neural circuits.”
(Source: ucsf.edu)
Exploring How the Nervous System Develops
The circuitry of the central nervous system is immensely complex and, as a result, sometimes confounding. When scientists conduct research to unravel the inner workings at a cellular level, they are sometimes surprised by what they find.
Patrick Keeley, a postdoctoral scholar in Benjamin Reese’s laboratory at UC Santa Barbara’s Neuroscience Research Institute, had such an experience. He spent years analyzing different cell types in the retina, the light-sensitive layer of tissue lining the inner surface of the eye that mediates the first stages of visual processing. The results of his research are published today in the journal Developmental Cell.
Using a rodent model, Keeley and his colleagues quantified the number of cells present in each retina for 12 different retinal cell types across 30 genetically distinct lines of mice. For every cell type the team investigated, the researchers found a remarkable degree of variation in cell number across the strains. More surprising, the variation in the number of different cell types was largely independent of one another across the strains. This has substantial implications for retinal wiring during cellular development.
“These cells are connected to each other, and their convergence ratios are believed to underlie various aspects of visual processing,” Keeley explained, “so it was expected that the numbers of these cell types might be correlated. But that was not the case at all. We found very few significant correlations and even the ones we did find were modest.”
Using quantitative trait locus (QTL) analysis — a statistical method that links two types of information, in this case cell number and genetic markers — Keeley’s team compared not only the covariance between different types of cells but also the genetic co-regulation of their number. When they mapped the variation in cell number to locations within the genome, the locations were rarely the same for different types of cells. The result was entirely unexpected.
“Current views of retinal development propose that molecular switches control the alternate fates a newborn neuron should adopt, leading one to expect negative correlations between certain cell types,” said Reese, who is also a professor in UCSB’s Department of Psychological and Brain Sciences. “Still others have proposed that synaptically connected nerve cells ‘match’ their pre- and post-synaptic numbers through a process of naturally occurring cell death, leading one to expect positive correlations between connected cell types. Neither expectation was borne out.”
“If the cell types are not correlated, then some mice will have retinas with a lot of one cell type — say, photoreceptors — but not a lot of another cell type to connect to, in this case bipolar cells, or vice versa,” Keeley added. “So how does the developing retina accommodate this variation?”
The authors posit that since the ratios of pre- to post-synaptic cell number are not precisely controlled, the rules for connecting them should offer a degree of plasticity as they wire their connections during development.
Take bipolar cells as an example. To test this assumption, the scientists looked at the morphology of their dendrites, the threadlike extensions of a neuron that gather synaptic input. Keeley and coworkers examined their size, their branching pattern and the number of contacts they formed as a function of the number of surrounding bipolar cells and the number of photoreceptors across these different strains.
“We found that the extent of dendritic growth was proportional to the local density of bipolar cells,” Keeley explained. “If there are more, they grow smaller dendrites. If there are fewer, they grow larger dendrites.
“Photoreceptor number, on the other hand, had no effect upon the size of the dendritic field of the bipolar cells but determined the frequency of branching made by those very dendrites,” he added. “This plasticity in neural circuit assembly ensures that the nervous system modulates its connectivity to accommodate the independent variation in cell number.”
This research gives scientists an idea of how individual cell types are generated, how they differentiate and how they form appropriate connections with one another. Researchers in the Reese lab are trying to understand the genes that control these processes.
“I think that’s important when we discuss cellular therapeutics such as transplanting stem cells to replace cells that are lost,” Keeley said. “We’re going to need this sort of fundamental knowledge about neural development to promote the differentiation and integration of transplanted stem cells. This focus on genetic and cellular mechanisms is going to be important for developing new therapies to treat developmental disorders affecting the eye.”
Unexpected origin for important parts of the nervous system
A new study from Karolinska Institutet shows that a part of the nervous system, the parasympathetic nervous system, is formed in a way that is different from what researchers previously believed. In this study, which is published in the journal Science, a new phenomenon is investigated within the field of developmental biology, and the findings may lead to new medical treatments for congenital disorders of the nervous system.
Almost all of the body’s functions are controlled by the autonomous, involuntary nervous system, for example the heart and blood vessels, liver and gastrointestinal system. At rest, the body is set up for energy saving functions, which is regulated by the parasympathetic part of the autonomous nervous system.
Current understanding is that many important types of cells, including the parasympathetic nerve cells in various organs, originate in early progenitor cells that move short distances while the embryo is still small. But this model does not explain how many of our organs – which develop relatively late, when the embryo is large – are furnished with cells that form the parasympathetic neurons.
This study alters a fundamental principal of our understanding of how the peripheral nervous system develops in the body. Researchers at Karolinska Institutet have made three-dimensional reconstructions of mouse embryos. These show that the parasympathetic neurons are formed from immature glial cells known as Schwann cell precursors that travel along the peripheral nerves out to the body’s tissues and organs. The immature cells have the properties of stem cells and may be the origin of several different types of cells. For example, the researchers behind this new study have previously demonstrated that the majority of our melanocytes (pigment cells) are born from these cells.
New principal of developmental biology
"Our study focuses on a new principal of developmental biology, a targeted recruitment of cells that are probably also used in the reconstruction of tissue. Despite the elegance, simplicity and beauty of this principal, it is still unclear how the number of parasympathetic neurons is controlled and why only some of the cells transported by nerves are transformed into that which becomes an important part of the nervous system", says Igor Adameyko at the Department of Physiology and Pharmacology who, together with Patrik Ernfors at the Department of Medical Biochemistry and Biophysics, is responsible for the study.
Somewhat surprisingly, the researchers found that the entire parasympathetic nervous system arises from these progenitor cells that travel along the peripheral nerves. The researchers hope that this discovery will open up the possibility of new ways to treat congenital disorders of the autonomous nervous system using regenerative medicine.
(Source: ki.se)
Research details how developing neurons sense a chemical cue
Symmetry is an inherent part of development. As an embryo, an organism’s brain and spinal cord, like the rest of its body, organize themselves into left and right halves as they grow. But a certain set of nerve cells do something unusual: they cross from one side to the other. New research in mice delves into the details of the molecular interactions that help guide these neurons toward this anatomical boundary.
In an embryo, a neuron’s branches, or axons, have special structures on their tips that sense chemical cues telling them where to grow. The new findings, by researchers at Memorial Sloan Kettering Cancer Center and The Rockefeller University, reveal the structural details of how one such cue, Netrin-1, interacts with two sensing molecules on the axons, DCC and a previously less well characterized player known as neogenin, as a part of this process.
“Our work provides the first high-resolution view of the molecular complexes that form on the surface of a developing axon and tell it to move in one direction or another,” says Dimitar Nikolov, a structural biologist at Memorial Sloan Kettering. “This detailed understanding of these assemblies helps us better understand neural wiring, and may one day be useful in the development of drugs to treat spinal cord or brain injuries.”
In a developing nervous system, the signaling molecule, Netrin-1, identified by Rockefeller University Professor Marc Tessier-Lavigne and colleagues, can guide neurons by attracting or repulsing them. In the case of axons that cross from one side to the other, extended by so-called commissural neurons, Netrin-1 attracts them toward the middle.
With a technique that uses X-rays to visualize the structure of crystalized proteins, research scientist Kai Xu and colleagues in Nikolov’s laboratory revealed that Netrin-1 has two separate binding sites on opposite ends, enabling it to simultaneously bind to different receptors. This may explain how Netrin-1, which is an important axon-guiding molecule, can affect in different ways neurons that express different combinations of receptors, Nikolov says.
For some time, scientists have known commissural neurons used the receptor molecule DCC to detect Netrin-1. Neogenin has a structure similar to DCC, and this research, described today in Science, confirms neogenin too acts as a sensing molecule for commissural neurons in mammals.
In experiments that complemented the structural work, conducted by Nicolas Renier and Zhuhao Wu in Tessier-Lavigne’s lab, the researchers confirmed that, like DCC, neogenin senses Netrin-1 for the growing commissural neurons in mice.
These neurons are part of the system by which one side of the brain controls movement on the opposite side of the body. As a result, a mutation in the gene responsible for DCC interferes with this coordination, causing congenital mirror movement disorder. People with this disorder cannot move one side of the body in isolation; for example, a right-handed wave is mirrored by a similar gesture by the left hand.
The work also has implications for understanding why DCC, neogenin and other cell-surface receptors come in slightly different forms, called splice isoforms. The structural research revealed these isoforms bind differently to Netrin-1. However, it is not yet clear what this means for neuron wiring, Nikolov says.
“With this structural knowledge, and with the identification of an additional receptor involved in axon guidance in the spinal cord, we are gaining deeper insight into the mechanisms through which neurons make connections that produce a functioning nervous system, as well as the dysfunction that arises from miswiring of connections” says Tessier-Lavigne.
(Source: newswire.rockefeller.edu)
With imprecise chips to the artificial brain
Which circuits and chips are suitable for building artificial brains using the least possible amount of power? This is the question that Junior Professor Dr. Elisabetta Chicca from the Center of Excellence Cognitive Interaction Technology (CITEC) has been investigating in collaboration with colleagues from Italy and Switzerland. A surprising finding: Constructions that use not only digital but also analog compact and imprecise circuits are more suitable for building artificial nervous systems, rather than arrangements with only digital or precise but power-demanding analog electronic circuits. The study will be published in the scientific journal ‘Proceedings of the IEEE’. A preview was published online on Thursday, 1 March 2014.
Elisabetta Chicca is the head of the research group ‘Neuromorphic Behaving Systems’. One of the aims of her work is to make robots and other technical systems as autonomous and capable of learning as possible. The artificial brains that she and her team are developing are modelled on the biological nervous systems of humans and animals. ‘Environmental stimuli are processed in the biological nervous systems of humans and animals in a totally different way to modern computers’, says Chicca. ‘Biological nervous systems organise themselves; they adapt and learn. In doing so, they require a relatively small amount of energy in comparison with computers and allow for complex skills such as decision-making, the recognition of associations and of patterns.’
The neuroinformatics researcher is trying to utilise biological principles to build artificial nervous systems. Dr. Chicca and her colleagues have been investigating which type of circuits can simulate synapses electronically. Synapses serve as the ‘bridges’ that transmit signals between nerve cells. Stimuli are communicated through them and they can also save information. Furthermore, the research team have analysed which type of circuit can imitate the so-called plasticity of the biological nerves. Plasticity describes the ability of nerve cells, synapses and cerebral areas to adapt their characteristics according to use. In the brains of athletes, for example, certain cerebral areas are more strongly connected than in non-athletes.
The four researchers also offer solutions for the control of artificial nervous systems. They present software on the basis of which programmes can be written that can control the circuits and chips of an ‘electronic brain’.
Scientists discover a protein in nerves that determines which brain connections stay and which go
A newborn baby, for all its cooing cuddliness, is a data acquisition machine, absorbing information to finish honing the job of brain wiring that started before birth. This is true nowhere more so than the eyes, which start life peering at a blurry world and within months can make out a crisp, three-dimensional image of a mobile dangling overhead.
This process of refining the brain’s wiring involves cutting off some of the excess nerve connections we have at birth while strengthening connections we use all the time. Some estimates show that as many as half of the brain’s connections formed during development are clipped back as the final wiring takes shape.
Carla Shatz, the David Starr Jordan Director of Stanford Bio-X, and her team, including postdoctoral researcher Hanmi Lee and Bio-X Graduate Fellow Jaimie Adelson, recently found a protein that is essential for the brain to remove those excess connections. The team specifically showed a role for the protein in the developing visual system in mice, but the work appears to apply broadly across the developing brain. They published their findings online March 30 in the journal Nature.
Shatz said the discovery helps clear up something that has been a mystery to those who study brain development: How does the decision get made to eliminate some connections? It also settles a decade-long debate over whether the nervous system or the immune system is making those decisions. (Spoiler alert: It’s the nervous system.)
A single vision
"Vision is a challenging problem because you have two eyes and only one view of the world," said Shatz, who is the Sapp Family Provostial Professor and professor of biology and of neurobiology. "There’s a very beautiful set of wiring steps that makes sure the eyes are pointed at the same place and the two images get aligned."
Shatz said the rule of which connections the brain cuts back to create that single vision follows a simple mantra: “Fire together, wire together. Out of sync, lose your link.” Or rather, if early in life the left sides of both eyes see the same duck motif wallpaper, those neurons fire together and stay linked up. When the top of one eye and bottom of the other eye form a connection, the nerves fire out of sync, and the connection weakens and is eventually pruned back. Over time, the only connections that remain are between parts of the two eyes that are seeing the same thing.
The ability to detect which nerves fire out of sync and should therefore lose their link requires the protein Shatz’s team reported, which goes by the name of MHC Class I D, or D for short. This protein is one that is famous for its role in the immune system, but only in the past decade has Shatz’s team started building a case for D’s independent role in the brain.
Two camps, one protein
In 2000 Shatz first published work suggesting that a group of immune proteins called MHC in mice and HLA in people played a role in the developing nervous system. At the time, this caused a stir among immunologists, who were surprised to find their proteins showing up in the brain.
Lawrence Steinman, professor of neurology and neurological sciences and of pediatrics at Stanford School of Medicine, has followed Shatz’s work from the perspective of both a neurologist and immunologist. “One of the reasons that I think the research is so interesting is that it shows us that molecules thought to be the province of one group can be in another,” he said, adding, “It slowed the prevailing idea that people believed that some molecules were the domain of one camp.”
Shatz is in the privileged position of directing Stanford Bio-X, which includes faculty members and students from both immunology and the neurological sciences. She said being able to talk about her work and collaborate with this mix of colleagues has helped break down barriers in thinking about her unexpected findings.
After the initial discovery, Shatz went on to show that two of those MHC proteins – D and its sister protein K – seemed to be important in eliminating connections in the brain. Mice genetically engineered to lack both K and D had poorly functioning immune systems and also ended up with the visual system in a jumble, with unrelated parts of the two eyes forming connections. Without D and K the mice weren’t detecting which connections fired out of sync, so those connections didn’t lose their link.
After Shatz published that work, some immunologists argued that perhaps D and K were necessary for brain remodeling only because of their key function in the immune system. “They were saying that the immune system was telling the nervous system what to prune,” Shatz said.
It was a theory, but not one Shatz agreed with. Her feeling was that just because D and K were first found in the immune system didn’t mean they couldn’t have a unique role in the brain. “The nervous system has just as much right to these immune proteins as the immune system,” Shatz said. Her most recent work makes that point clear.
D on the brain
Shatz and her group worked with the mice that were lacking D and K everywhere, then used genetic engineering tricks to add D back, but only in the neurons. These mice still had poorly functioning immune systems, but had perfectly normal eye connections. In these mice, the nerves were able to determine which connections to cut and which to keep, even without the immune system.
Steinman said the work settles the issue of whether D is acting in the brain separate from its role in the immune system. “If Carla had studied MHC proteins before the immunologists, then we would consider them to be part of the nervous system. They clearly have major roles in both the nervous system and the immune system,” he said.
The group went on to show that the presence of D alters the composition of other proteins on the nerve cell surface that are in charge of receiving signals from other nerves. Her team thinks that it is this difference in how the nerve receives signals with or without D that makes the pruning process go awry.
Essentially, without D all nerve connections appear to be firing together and therefore they stay wired together.
Shatz says that in addition to explaining an important part of brain development, the work could also provide a new avenue for studying schizophrenia. Some studies have shown that people with mutations in the human genes related to D (called HLA genes) are more prone to the disease. Other studies have associated schizophrenia with improperly formed connections in the brain. Shatz suggests that this new role for D in the brain could mean that the pruning process has gone awry in schizophrenia. The group plans to explore this idea further, as well as to tease apart what D is doing to alter the composition of neurotransmitter receptors on the nerve cell surface.
Vast gene-expression map yields neurological and environmental stress insights
A consortium led by scientists from the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) has conducted the largest survey yet of how information encoded in an animal genome is processed in different organs, stages of development, and environmental conditions. Their findings paint a new picture of how genes function in the nervous system and in response to environmental stress.
They report their research this week in the Advance Online Publication of the journal Nature.
The scientists studied the fruit fly, an important model organism in genetics research. Seventy percent of known human disease genes have closely related genes in the fly, yet the fly genome is one-thirtieth the size of ours. Previous fruit fly research has provided insights on cancer, birth defects, addictive behavior, and neurological diseases. It has also advanced our understanding of processes common to all animals such as body patterning and synaptic transmission.
In the latest scientific fruit from the fruit fly, the consortium, led by Susan Celniker of Berkeley Lab’s Life Sciences Division, generated the most comprehensive map of gene expression in any animal to date. Scientists from the University of California at Berkeley, Indiana University at Bloomington, the University of Connecticut Health Center, and several other institutions contributed to the research.
Immune System Has Dramatic Impact on Children’s Brain Development
New research from the University of Virginia School of Medicine has revealed the dramatic effect the immune system has on the brain development of young children. The findings suggest new and better ways to prevent developmental impairment in children in developing countries, helping to free them from a cycle of poverty and disease, and to attain their full potential.
U.Va. researchers working in Bangladesh determined that the more days infants suffered fever, the worse they performed on developmental tests at 12 and 24 months. They also found that elevated levels of inflammation-causing proteins in the blood were associated with worse performance, while higher levels of inflammation-fighting proteins were associated with improved performance.
“The problem we sought to address was why millions of young children in low- and middle-income countries are not attaining their full developmental potential,” said lead author Nona Jiang, who performed the research while an undergraduate student in the laboratory of Dr. William Petri Jr. “Early childhood is an absolutely critical time of brain development, and it’s also a time when these children are suffering from recurrent infections. Therefore, we asked whether these infections are contributing to the impaired development we observe in children growing up in adversity.”
Their findings offer a potential explanation for the developmental impairment seen in children living in poverty. They also offer important direction for doctors attempting to combat the problem: By preventing inflammation, physicians may be able to enhance children’s mental ability for a lifetime.
“We are interested in examining factors that predict healthy child development around the world,” said researcher Dr. Rebecca Scharf of U.Va.’s Department of Pediatrics. “By studying which early childhood influences are associated with hindrances to growth and learning, we will know better where to target interventions for the critical period of early childhood.”
In addition, the finding illuminates the complex relationship between the immune system and cognitive development, an increasingly important area of research that U.Va. has helped pioneer.
“This is a very interesting study, showing, probably for the first time, the link between peripheral cytokine levels and improved cognitive development in humans,” said Jonathan Kipnis, a professor of neuroscience and director of U.Va.’s Center for Brain Immunology & Glia. “What is of the most interest and of a great novelty is the fact that [inflammation-fighting cytokines] have positive correlation with cognitive function. My lab published results showing that these IL-4 cytokines are required for proper brain function in mice, and this work from Dr. Petri’s lab completely independently shows similar correlation in humans.
“I hope the scientific community will appreciate how dramatic the effects of the immune system are on the central nervous system and will invest more efforts in studying and better understanding these complex and intriguing interactions between the body’s two major systems.”
(Source: news.virginia.edu)