Posts tagged nerve cells
Articles and news from the latest research reports.
One neuron has huge impact on brain behaviour
Researchers from Queensland and the USA have made a unique discovery about how the brain computes sensory information.
The study by scientists at the Queensland Brain Institute (QBI) at The University of Queensland (UQ) and the Howard Hughes Medical Institute in the USA was conducted to better understand how circuits of nerve cells underlie behaviour.
Using advanced optical imaging in animal models, the research team was able to pinpoint a single neuron in the neocortex that signaled sensory behavior. This led to the discovery that active processes in its thin dendritic appendages are responsible for implementing the integration of sensory and motor signals.
“We have long known that active dendrites provide neurons with powerful processing capabilities,” says QBI’s Associate Professor Stephen Williams, who collaborated on the study. “However, little has been known about the role of neuronal dendrites in behaviourally related circuit computations. “We were pleasantly surprised to discover that the dendrites of nerve cells operate during behaviour to implement the integration of sensory and motor signals,” he said.
Such multi-modal integration enables the brain to perform at lightning speed, allowing animals to react to their environment in relation to existing knowledge. The paper, titled ‘Nonlinear dendritic integration of sensory and motor input during an active sensing task’ was published in the prestigious journal, Nature.
Engineering a Photo-Switch for Nerve Cells in the Eye and Brain
Chemists and vision scientists at the University of Illinois at Chicago have designed a light-sensitive molecule that can stimulate a neural response in cells of the retina and brain — a possible first step to overcoming degenerative eye diseases like age-related macular degeneration, or to quieting epileptic seizures.
Their results are reported online in the journal Nature Communications.
Macular degeneration, the leading cause of vision loss in people over 50, is caused by loss of light-sensitive cells in the retina — the rods and cones.
"The rods and cones, which absorb light and initiate visual signals, are the broken link in the chain, even though what we call the ‘inner cells’ of the retina, in many cases, are still potentially capable of function," says David Pepperberg, professor of ophthalmology and visual sciences in the UIC College of Medicine, the principal investigator on the study.
"Our approach is to bypass the lost rods and cones, by making the inner cells responsive to light."
Pepperberg and his colleagues are trying to develop light-sensitive molecules that — when injected into the eye — can find their way to inner retinal cells, attach themselves, and initiate the signal that is sent to the brain.
Key protein interactions involved in neurodegenerative disease revealed
Scientists from the Florida campus of The Scripps Research Institute (TSRI) have defined the molecular structure of an enzyme as it interacts with several proteins involved in outcomes that can influence neurodegenerative disease and insulin resistance. The enzymes in question, which play a critical role in nerve cell (neuron) survival, are among the most prized targets for drugs to treat brain disorders such as Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis (ALS).
The study was published online ahead of print on November 8, 2012, by the journal Structure.
The new study reveals the structure of a class of enzymes called c-jun-N-terminal kinases (JNK) when bound to three peptides from different protein families; JNK is an important contributor to stress-induced apoptosis (cell death), and several studies in animal models have shown that JNK inhibition protects against neurodegeneration.
"Our findings have long-range implications for drug discovery," said TSRI Professor Philip LoGrasso, who, along with TSRI Associate Professor Kendall Nettles, led the study. "Knowing the structure of JNK bound to these proteins will allow us to make novel substrate competitive inhibitors for this enzyme with even greater specificity and hopefully less toxicity."
The scientists used what they called structure class analysis, looking at groups of structures, which revealed subtle differences not apparent looking at them individually.
"From a structural point of view, these different proteins appear to be very similar, but the biochemistry shows that the results of their binding to JNK were very different," he said.
LoGrasso and his colleagues were responsible for creating and solving the crystal structures of the three peptides (JIP1, SAB, and ATF-2) with JNK3 using a technique called x-ray crystallography, while Nettles handled much of the data analysis.
All three peptides have important effects, LoGrasso said, inducing two distinct inhibitory mechanisms—one where the peptide caused the activation loop to bind directly in the ATP pocket, and another with allosteric control (that is, using a location on the protein other than the active site). Because JNK signaling needs to be tightly controlled, even small changes in it can alter a cell’s fate.
"Solving the crystal structures of these three bound peptides gives us a clearer idea of how we can block each of these mechanisms related to cell death and survival," LoGrasso said. "You have to know their structure to know how to deal with them."
(Source: medicalxpress.com)
Unique spinal nerve cell activity discovery
Scientists from the University of Leicester have hit upon unique forms of spinal nerve activity that shape output of nerve cell networks controlling motor behaviours.
The breakthrough in the Department of Biology at the University of Leicester is announced in the journal Current Biology. The three-year study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC).
Although the neural basis of motor control has been studied for over a century, the processes controlling maturation of locomotor behaviours – like walking and swimming - are not fully understood.
The University of Leicester research into nerve cells responsible for motor behaviours was carried out on fish. The team aimed to understand how spinal networks produce rhythmic activity from a very immature stage - and how such activity changes during maturation.
The team used zebrafish, a freshwater fish native to northern India and Bangladesh, because their motor networks are similar to humans. However, as they are fertilized outside the mother and their embryos are transparent, scientists can readily monitor motor network development from its onset - something that is very difficult to do in mammals.
Stem cells + nanofibers = promising nerve research
Every week in his clinic at the University of Michigan, neurologist Joseph Corey, M.D., Ph.D., treats patients whose nerves are dying or shrinking due to disease or injury.
He sees the pain, the loss of ability and the other effects that nerve-destroying conditions cause – and wishes he could give patients more effective treatments than what’s available, or regenerate their nerves. Then he heads to his research lab at the VA Ann Arbor Healthcare System, where his team is working toward that exact goal.
In new research published in several recent papers (Nature Methods, Biomacromolecules, Materials Science and Engineering) Corey and his colleagues from the U-M Medical School, VAAAHS and the University of California, San Francisco report success in developing polymer nanofiber technologies for understanding how nerves form, why they don’t reconnect after injury, and what can be done to prevent or slow damage.
Using polymer nanofibers thinner than human hairs as scaffolds, researchers coaxed a particular type of brain cell to wrap around fibers that mimic the shape and size of nerves found in the body.
They’ve even managed to encourage the process of myelination – the formation of a protective coating that guards larger nerve fibers from damage. They began to see multiple concentric layers of the protective substance called myelin start to form, just as they do in the body.
(Source: uofmhealth.org)
Discovery may help nerve regeneration in spinal injury
Scientists at the Universities of Liverpool and Glasgow have uncovered a possible new method of enhancing nerve repair in the treatment of spinal cord injuries.
It is known that scar tissue, which forms following spinal cord injury, creates an impenetrable barrier to nerve regeneration, leading to the irreversible paralysis associated with spinal injuries. Scientists at Liverpool and Glasgow have discovered that long-chain sugars, called heparan sulfates, play a significant role in the process of scar formation in cell models in the laboratory.
Research findings have the potential to contribute to new strategies for manipulating the scarring process induced in spinal cord injury and improving the effectiveness of cell transplantation therapies in patients with this type of injury.
Scarring occurs due to the activation, change in shape, and stiffness of cells, called astrocytes, which are the major nerve support cells in the spinal cord. One possible way to repair nerve damage is transplantation of support cells from peripheral nerves, called Schwann cells. The team, however, found that these cells secrete heparan sulfate sugars, which promote scarring reactions and could reduce the effectiveness of nerve repair.
Scientists showed that these sugars can over-activate protein growth factors that promote astrocyte scarring. Significantly, however, they found this over-activation could be inhibited by chemically modified heparins made in the laboratory. These compounds could prevent the scarring reaction of astrocyte cells, opening up new opportunities for treatment of damaged nerve cells.
Professor Jerry Turnbull, from the University of Liverpool’s Institute of Integrative Biology, said: “Spinal injury is a devastating condition and can result in paralysis for life. The sugars we are investigating are produced by nearly every cell in the body, and are similar to the blood thinning drug heparin.
"We found that some sugar types promote scarring reaction, but remarkably other types, which can be chemically produced in the laboratory by modifying heparin, can prevent this in our cell models.
"Studies in animal cells are now needed, but the exciting thing about this work is that it could, in the future, provide a way of developing treatments for improving nerve repair in patients, using the body’s own Schwann cells, supplemented with specific sugars."
Professor Sue Barnett, from the University of Glasgow’s Institute of Infection, Immunity and Inflammation, said: “We had already shown that Schwann cells, identified as having the potential to promote nerve regrowth, induced scarring in spinal cord injury. Now that we know that they secrete these complex sugars, which lead to scarring, we have the opportunity to intervene in this process, and promote central nervous system repair.”
(Source: eurekalert.org)
Researchers identify gene required for nerve regeneration
A gene that is associated with regeneration of injured nerve cells has been identified by scientists at Penn State and Duke University. The team, led by Melissa Rolls, an assistant professor of biochemistry and molecular biology at Penn State, has found that a mutation in a single gene can entirely shut down the process by which axons — the parts of the nerve cell that are responsible for sending signals to other cells — regrow themselves after being cut or damaged. “We are hopeful that this discovery will open the door to new research related to spinal-cord and other neurological disorders in humans,” Rolls said. The journal Cell Reports published an early online copy of the paper (Nov. 1), and also will include the paper in the monthly issue of the journal, which will be published Nov. 29.
Stay-at-home transcription factor saves axons
The old saw that local actions can have global consequences holds true for neurons, too. Selvaraj et al. show that a transcription factor remains in the axon to help prevent neurodegeneration.
In neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), neurons usually die in stages, with axons deteriorating first and the cells themselves perishing later. Axon degeneration may represent a turning point for patients, after which so much neuronal damage has accumulated that treatments won’t work. Researchers have tested several proteins for their ability to save axons. One of these molecules, ciliary neurotrophic factor (CNTF), rescues axons in rodents and extends their lives. But it caused severe side effects in patients during clinical trials. “Acting on the same pathway but farther downstream could be an ideal way to improve the situation for motor neuron disease” and possibly for other neurodegenerative diseases, says senior author Michael Sendtner.
To discover how CNTF works, Selvaraj et al. studied pmn mutant mice that mimic ALS. The researchers found that CNTF not only prevented the shrinkage of the rodents’ motor neurons, it also reduced the number of swellings along the axon that are markers of degeneration. Another sign that CNTF was beneficial was the movement of mitochondria, which continually shuttle back and forth along the axons of healthy motor neurons. In axons from pmn mice, stalled mitochondria were prevalent, but treatment with CNTF accelerated the organelles to normal speeds.
Stimulating brain cells with light
Introducing a light-sensitive protein in transgenic nerve cells… transplanting nerve cells into the brains of laboratory animals… inserting an optic fibre in the brain and using it to light up the nerve cells and stimulate them into releasing more dopamine to combat Parkinson’s disease… These events may sound like science fiction but they are soon to become a reality in a research laboratory at Lund University in Sweden.
For the time being, this is basic research but the long term objective is to find new ways of treating Parkinson’s disease. This increasingly common disease is caused by degeneration of the brain cells producing signal substance dopamine.
Many experiments have been conducted on both animals and humans, transplanting healthy nerve cells to make up for the lack of dopamine, but it is difficult to study what happens to the transplant.
“We don’t know how the new nerve cells behave once they have been transplanted into the brain. Do they connect to the surrounding cells as they should, and can they function normally and produce dopamine as they should? Can we use light to reinforce dopamine production? These are the issues we want to investigate with optogenetics”, says Professor Merab Kokaia.
Optogenetics allows scientists to control certain cells in the brain using light, leaving other cells unaffected. In order to do this, the relevant cells are equipped with genes for a special light-sensitive protein. The protein makes the cells react when they are illuminated with light from a thin optic fibre which is also implanted in the brain. The cells can then be “switched on” when they are illuminated.
“If we get signals as a response to light from the host brain, we know that they come from the transplanted cells since they are the only ones to carry the light-sensitive protein. This gives us a much more specific way of studying the brain’s reactions than inserting an electrode, which is the current method. With an electrode, we do not know whether the electric signals that are detected come from “new” or “old” brain cells”, explains Merab Kokaia.
The work will be conducted on laboratory rats modelling Parkinson’s disease. The transplanted cells will be derived from skin from an adult human and will have been “reprogrammed” as nerve cells. Merab Kokaia will be collaborating with neuro-researchers Malin Parmar and Olle Lindvall on the project.
The three Lund researchers have received a grant of USD 75 000 from the Michael J. Fox Foundation, started by actor Michael J. Fox and dedicated to Parkinson’s research.
The light-sensitive protein is obtained from a bacterium, which uses light to gain energy. Since it is not a human protein, the safety checks will be extra strict if the method is to be used on humans.
”We know that this is long term research. But the methodology is interesting and it will be exciting to see what we can come up with,” says Merab Kokaia.
(Source: lunduniversity.lu.se)
Researchers at the doorstep of stem cell therapies for MS, other myelin disorders
When the era of regenerative medicine dawned more than three decades ago, the potential to replenish populations of cells destroyed by disease was seen by many as the next medical revolution. However, what followed turned out not to be a sprint to the clinic, but rather a long tedious slog carried out in labs across the globe required to master the complexity of stem cells and then pair their capabilities and attributes with specific diseases.
In a review article appearing today in the journal Science, University of Rochester Medical Center scientists Steve Goldman, M.D., Ph.D., Maiken Nedergaard, Ph.D., and Martha Windrem, Ph.D., contend that researchers are now on the threshold of human application of stem cell therapies for a class of neurological diseases known as myelin disorders – a long list of diseases that include conditions such as multiple sclerosis, white matter stroke, cerebral palsy, certain dementias, and rare but fatal childhood disorders called pediatric leukodystrophies.
"Stem cell biology has progressed in many ways over the last decade, and many potential opportunities for clinical translation have arisen," said Goldman. "In particular, for diseases of the central nervous system, which have proven difficult to treat because of the brain’s great cellular complexity, we postulated that the simplest cell types might provide us the best opportunities for cell therapy."
The common factor in myelin disorders is a cell called the oligodendrocyte. These cells arise, or are created, by another cell found in the central nervous system called the glial progenitor cell. Both oligodendrocytes and their “sister cells” – called astrocytes – share this same parent and serve critical support functions in the central nervous systems.
(Source: eurekalert.org)