Johns Hopkins scientists say they have evidence from animal studies that a type of central nervous system cell other than motor neurons plays a fundamental role in the development of amyotrophic lateral sclerosis (ALS), a fatal degenerative disease. The discovery holds promise, they say, for identifying new targets for interrupting the disease's progress.
In a study described online in Nature Neuroscience, the researchers found that, in mice bred with a gene mutation that causes human ALS, dramatic changes occurred in oligodendrocytes cells that create insulation for the nerves of the central nervous system long before the first physical symptoms of the disease appeared. Oligodendrocytes located near motor neurons cells that govern movement died off at very high rates, and new ones regenerated in their place were inferior and unhealthy.
The researchers also found, to their surprise, that suppressing an ALS-causing gene in oligodendrocytes of mice bred with the disease while still allowing the gene to remain in the motor neurons profoundly delayed the onset of ALS. It also prolonged survival of these mice by more than three months, a long time in the life span of a mouse. These observations suggest that oligodendrocytes play a very significant role in the early stage of the disease.
"The abnormalities in oligodendrocytes appear to be having a negative impact on the survival of motor neurons," says Dwight E. Bergles, Ph.D., a co-author and a professor of neuroscience at the Johns Hopkins University School of Medicine. "The motor neurons seem to be dependent on healthy oligodendrocytes for survival, something we didn't appreciate before."
"These findings teach us that cells we never thought had a role in ALS not only are involved but also clearly contribute to the onset of the disease," says co-author Jeffrey D. Rothstein, M.D., Ph.D., a professor of neurology at Johns Hopkins and director of the Johns Hopkins Medic
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Johns Hopkins Medicine