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

Oligodendrocytes form myelin sheaths and provide metabolic support to axons. Using in vivo genetic fate tracing in a mouse model of amyotrophic lateral sclerosis (ALS), this study shows that there is extensive degeneration of oligodendrocytes near motor neurons prior to behavioral manifestation of disease. Although oligodendrocytes were regenerated from resident progenitors, they failed to mature and restore myelin, a feature also observed in brain and spinal cord tissue from ALS patients. Selective deletion of ALS-linked mutant SOD1 from the oligodendrocyte lineage greatly delayed disease onset, suggesting that this mutant protein impairs their ability to support motor neurons.