Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis

Shin H. Kang, Ying Li, Masahiro Fukaya, Ileana Lorenzini, Don W. Cleveland, Lyle Ostrow, Jeffrey D Rothstein, Dwight E Bergles

Research output: Contribution to journalArticle

Abstract

Oligodendrocytes associate with axons to establish myelin and provide metabolic support to neurons. In the spinal cord of amyotrophic lateral sclerosis (ALS) mice, oligodendrocytes downregulate transporters that transfer glycolytic substrates to neurons and oligodendrocyte progenitors (NG2 + cells) exhibit enhanced proliferation and differentiation, although the cause of these changes in oligodendroglia is unknown. We found extensive degeneration of gray matter oligodendrocytes in the spinal cord of SOD1 (G93A) ALS mice prior to disease onset. Although new oligodendrocytes were formed, they failed to mature, resulting in progressive demyelination. Oligodendrocyte dysfunction was also prevalent in human ALS, as gray matter demyelination and reactive changes in NG2 + cells were observed in motor cortex and spinal cord of ALS patients. Selective removal of mutant SOD1 from oligodendroglia substantially delayed disease onset and prolonged survival in ALS mice, suggesting that ALS-linked genes enhance the vulnerability of motor neurons and accelerate disease by directly impairing the function of oligodendrocytes.

Original languageEnglish (US)
Pages (from-to)571-579
Number of pages9
JournalNature Neuroscience
Volume16
Issue number5
DOIs
StatePublished - May 2013

    Fingerprint

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this