By tracking the fate of a group of immature cells that persist in the adult brain and spinal cord, Johns Hopkins researchers discovered in mice that these cells undergo dramatic changes in ALS, also known as Lou Gehrig's disease.
A study reported November 17 online in Neuron shows that these cells, called NG2+, grow and expand rapidly during early life, eventually morphing into mature nervous system cells called oligodendrocytes. These "oligos" help speed the transmission of electrical impulses by providing insulation around nerve cells. This insulation, known as myelin, is disrupted in nervous system diseases such as multiple sclerosis.
The team tracked the fate of NG2+ cells in both normal mice and mice with a mutant form of the SOD1 gene that causes ALS. Using a stringent system that let them color-tag only NG2+ cells and then accurately locate these cells at various times in their development, the researchers found that NG2+ cells normally keep up a quiet program of dividing in adult tissues, sometimes replacing themselves and other times forming new oligos.
A slow and steady turnover of oligodendrocytes may be required throughout life to maintain myelin, says Dwight Bergles, Ph.D., associate professor in The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine. However, the normal developmental program of NG2+ cells goes awry in the spinal cords of ALS mice.
"In the model ALS mice we studied, it's as though NG2+ cells step onto a high-speed treadmill," Bergles says. "They undergo explosive division, morph more readily into abnormal-looking oligodendrocytes and then, uncharacteristically, those differentiated cells quickly die. The brakes that normally hold these cells in check appear to be gone in ALS."
Of special note are provocative data showing this cell type as the most proliferating cell population in the spinal cords of ALS mice, churning out even more oligodendrocyt
|Contact: Maryalice Yakutchik|
Johns Hopkins Medical Institutions