Glial Precursor Cells May Play a Role in ALS

A new study has identified a group of immature cells that persist in the adult brain and spinal cord that undergo dramatic changes in amyotrophic lateral sclerosis (ALS), and could lead to new insights on the disease.

Researchers at Johns Hopkins University (JHU; Baltimore, MD, USA) examined an omnipresent population of glial progenitors known as NG2+, a line of cells that have the ability to develop into oligodendrocytes, and in addition which undergo dramatic changes in response to injury and demyelination. The researchers tracked the fate of the NG2+ cells in both normal mice and mice with a mutant form of the gene that causes ALS, and found that NG2+ cells in the postnatal central nervous system (CNS) generate myelinating oligodendrocytes, but not astrocytes or neurons.

According to the researchers, these results indicate that NG2+ cells in the normal CNS are oligodendrocyte precursors with restricted lineage potential, and that cell loss and gliosis are not sufficient to alter the lineage potential of these progenitors. However, in regions of neuro-degeneration in the spinal cord of the ALS mice, the NG2+ cells exhibited enhanced proliferation and accelerated differentiation into oligodendrocytes, although remaining committed to the oligodendrocyte lineage. The study was published early online on November 17, 2010, in Neuron.

"In the model ALS mice we studied, it's as though NG2+ cells step onto a high-speed treadmill,” said lead author Dwight Bergles, PhD, an associate professor in the JHU department of neuroscience. "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.”

"This goes much further than simply confirming a negative finding about these mysterious cells,” added coauthor Shin Kang, PhD. "We've answered a question, but the new observation about the overgrowth could lead to an entirely new understanding of ALS.”

Oligodendrocytes are cells that help speed the transmission of electrical impulses by providing the myelin sheath insulation surrounding nerve cells. Their main function is the insulation of axons in the CNS of higher vertebrates. A single oligodendrocyte can extend its processes to 50 axons, wrapping around approximately 1 mm of myelin sheath around each axon.

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