Johns Hopkins researchers during a study on mice, found that a group of immature cells which persist in the adult brain and spinal cord undergo dramatic changes in Lou Gehrig's disease.
Their study 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, 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 said.
"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 oligodendrocytes than in normal mice, says Shin Kang, a research associate in The Solomon H. Snyder Department of Neuroscience.
"This suggests there is significant oligodendrocyte death even before anything else degenerates," he explained, "which identifies a new and important player in the progression of this disease."
All this frenetic oligodendrocyte-generating activity takes place in the central nervous system's gray matter where other cells - the motor neurons - are dying. A body of research shows that after acute trauma to the central nervous system, a short-term upswing in NG2 activity takes place that may help reduce the extent of damage. Whether this change in behavior of NG2+ cells is protective, or accelerates the death of motor neurons in ALS, is not yet known.
The research has been published online in Neuron.