Oligodendrocyte progenitor cells are promoted in the neurogenic niches of the juvenile mouse brain during viral infection

Background Viruses can profoundly disturb myelination in the brain, leading to enduring neurological sequelae. The outcomes of neurotropic infections can be especially dire in younger children, in whom developmental myelination is underway. In some adult models of viral infection, demyelination is immune-mediated; however, it is unclear how an antiviral immune response impacts myelination in the young brain. Methods We investigated the outcomes of a neuron-restricted viral infection on developmental myelination in juvenile mice (10 days old), where only mature neurons are infectable by measles virus (MeV). The impact of neuronal MeV infection and the ensuing antiviral immune response on myelination was assessed during acute infection (9 days post-infection, dpi) and afterwards in surviving mice (90 dpi). We quantified myelin proteins and lipids in multiple brain regions, assessed oligodendrocyte development from the oligodendrocyte progenitor (OPC) stage to maturity, and measured neuronal markers associated with appropriate myelination and synapse formation. Results We found that (a) neuron-restricted viral infection was associated with short-term disruptions in myelin lipids and long-term disruptions in myelin proteins in multiple brain regions; (b) the OPC pool expanded in the neurogenic niches of the brain both during and after acute infection; (c) the expansion in the OPC pool originated from increased differentiation by neural stem cells (NSCs) rather than OPC proliferation; (d) oligodendrocyte maturation increased despite diminished myelination; and (e) expression of axonal and synaptic markers were compromised in surviving mice, although neuronal numbers were maintained in the hippocampus. Conclusions Our findings show a robust OPC response in the juvenile brain during viral infection, but this response ultimately fails to normalize myelination and neuronal markers in surviving mice. We speculate that these mechanisms partly underlie life-long neurological impairments in some survivors of childhood infections.