OL dysfunction/loss is now implicated in contributing to a wide array of neurological/psychiatric disorders. Pathogenesis of multiple system atrophy (MSA), characterized by a variable combination of parkinsonism, cerebellar impairment, and autonomic dysfunction, is ascribed to the accumulation of aggregated α-synuclein in OLs, which leads to severe neuronal loss, yet only a modest reduction in OLs20,21. Studies of the leukodystrophy Vanishing White Matter disease, in which mutations occur in subunits comprising the eukaryotic initiation factor 2B (eIF2B), demonstrate OL-directed cytotoxic function of astrocytes for reasons that are not completely understood22. Acquired pathology of OLs is also described in Parkinson’s Disease23, Alzheimer’s Disease24, and social isolation syndromes25,26, and dysfunctional OL-neuron interactions during development are described in Schizophrenia and Autism Spectrum Disorders27–29. There is evidence for varying susceptibility to injury based on the maturity of OL lineage cells. For instance, mature OLs are relatively preserved following perinatal white matter injury (e.g., periventricular leukomalacia, hypoxic-ischemic encephalopathy) in response to inflammatory and/or hypoxic-ischemic damage, as opposed to late-stage OL progenitors being highly susceptible to oxidative stress-induced apoptosis30. In addition, our analysis of MS tissues indicated a relatively greater loss of progenitors than mature OLs within active MS lesions31.
