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Molecular Partners Required For Appropriate Neuronal Gene Repression

frequently found in limited amounts in the brains of both healthy mice and humans. However, instead of developing tumors, the mice with elevated CD44 developed tremors similar to those seen in individuals with multiple sclerosis (MS).

Further investigation revealed that the tremors were associated with the loss of myelin sheaths on nerve cells, very similar to the myelin loss associated with MS and other neurological diseases, as well as in premature infants. In addition, Sherman's lab found large amounts of hyaluronic acid (HA), a carbohydrate, in the brains of these mice. A comparison to brain tissue of deceased human MS patients also revealed heightened levels of HA, apparently caused by the increased presence of CD44 -- something which had never been noted before. It was at this point that Sherman contacted Bebo, who had been studying an MS-like disease in mice for many years, and they began a collaboration to study how HA accumulated in regions of the nervous system where myelin had been destroyed.

"These investigations revealed that oligodendrocytes, which are cells that form myelin in the brain, were prevented from repairing the damaged myelin when there were elevated levels of HA," explained Bebo. "By studying another mouse model in my lab, we made the connection between heightened levels of HA -- specifically a high-molecular weight version of HA -- and myelin loss in an MS-like disease in mice. We also identified the cells that were making the HA and determined that HA accumulation was linked to an overabundance of the CD44 protein."

To further understand the process, Bebo and Sherman joined forces with Back, a pediatric neurologist and researcher studying developmental brain injury in premature infants. Previous research by Back and other scientists had revealed a link between the white matter brain damage associated with premature birth and damage to immature cells in the brain and spinal cord, called oligodendrocyte progenitors.
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