Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein lets brain repair damage from multiple sclerosis, other disorders

08.06.2010
A protein that helps build the brain in infants and children may aid efforts to restore damage from multiple sclerosis (MS) and other neurodegenerative diseases, researchers at Washington University School of Medicine in St. Louis have found.

In a mouse model of MS, researchers found that the protein, CXCR4, is essential for repairing myelin, a protective sheath that covers nerve cell branches. MS and other disorders damage myelin, and this damage is linked to loss of the branches inside the myelin.

"In MS patients, myelin repair occurs inconsistently for reasons that aren't clear," says senior author Robyn Klein, MD, PhD, associate professor of medicine and of neurobiology. "Understanding the nature of that problem is a priority because when myelin isn't repaired, the chances that an MS flare-up will inflict lasting harm seem to increase."

The findings appear online in The Proceedings of the National Academy of Sciences.

Mouse models typically mimic MS symptoms by causing chronic immune cell infiltration in the brain, but, according to Klein, the ongoing immune damage caused by the cells makes it difficult for researchers to focus on what the brain does to repair myelin.

For the study, Klein and first author and postdoctoral fellow Jigisha Patel, PhD, used a non-inflammatory model that involves giving mice food containing cuprizone, a compound that causes the death of cells that form myelin in the central nervous system. After six weeks, these cells, known as oligodendrocytes, are dead, and the corpus callosum, a structure that connects the left and right hemispheres of the brain, has lost its myelin. If cuprizone is then removed from the mouse diet, new cells migrate to the area that restore the myelin by becoming mature oligodendrocytes.

Klein's investigations began with the processes triggered by dying oligodendrocytes while mice are still on the cuprizone diet. The dying cells activate other support cells in the brain, causing them to express inflammatory factors.

Klein showed that levels of a receptor for inflammatory factors, CXCR4, peaked at six weeks. If researchers continued feeding the mice cuprizone for 12 weeks, levels of the inflammatory factor and its receptor dropped significantly. At 12 weeks the mice were also unable to restore myelin, suggesting a potential connection between myelin repair and CXCR4.

"This was a surprise, because the main thing CXCR4 has been known for is its role in forming the brain, not healing the brain," Klein says. "But we did know that injury increases the number of brain cells that make CXCR4, so it wasn't an unreasonable place to look."

Klein showed that the cells destined to become oligodendrocytes and repair myelin damage, known as neural precursor cells, have high levels of the CXCR4. The cells come up to the corpus callosum from an area below the ventricles, a noncellular area filled with cerebrospinal fluid.

When scientists blocked CXCR4 from becoming activated or reduced cells' ability to make it, the mice were unable to restore myelin. Neural precursor cells stayed in the ventricle and grew in number but did not move to the corpus callosum to begin repairs.

"Apparently the neural precursor cells have to stop proliferating before they can migrate, and CXCR4 plays a role in this change," Klein says. "CXCR4 also seems to be essential to the cells' ability to develop into mature oligodendrocytes and form myelin."

Klein plans to see if she can restore myelin repair in genetically engineered mouse models of MS with a genetically altered lentivirus that increases levels of an inflammatory factor that activates CXCR4. She also will work with Washington University colleagues to study the new model with advanced imaging techniques in an attempt to further clarify the relationship between loss of nerve cell branches and myelin damage in MS.

"We do not yet know if this myelin repair pathway is somehow damaged or impaired in MS patients," Klein says. "But I like the idea of turning on something that the brain already knows how to make by itself, allowing it to heal itself with its own molecules."

Patel JR, McCandless EE, Dorsey D, Klein RS. CXCR4 promotes differentiation of oligodendrocytes progenitors and remyelination. Proceedings of the National Academy of Sciences, published online May 31, 2010.

Funding from the National Institutes of Health and the National Institute of Neurological Disorders and Stroke supported this research.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Michael C. Purdy | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht Study shines light on brain cells that coordinate movement
26.06.2017 | University of Washington Health Sciences/UW Medicine

nachricht New insight into a central biological dogma on ion transport
26.06.2017 | Aarhus University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Study shines light on brain cells that coordinate movement

26.06.2017 | Life Sciences

Smooth propagation of spin waves using gold

26.06.2017 | Physics and Astronomy

Switchable DNA mini-machines store information

26.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>