Perturbations in neural stem cell function during a neurotropic viral infection in juvenile mice

Viral infections of the central nervous system (CNS) often cause worse neurological outcomes in younger hosts. Throughout childhood, the brain undergoes extensive development and refinement to produce functional neural networks. Network function is maintained partly with the help of neural stem cells (NSCs) that replace neuronal and glia subtypes in the two neurogenic niches of the brain (the hippocampus and subventricular zone). Accumulating evidence suggests that viruses disrupt NSC function in adulthood and infancy, but the in vivo impact of childhood infections on acute and long-term NSC function is unknown. Using a juvenile mouse model of measles virus (MeV) infection, where only mature neurons in the brain are infected, we defined the effects of the antiviral immune response on NSCs from juvenile to adult stages of life. We found that (a) virus persists in the brains of survivors despite an anti-viral immune response; (b) NSC numbers decrease dramatically during early infection, but ultimately stabilize in adult survivors; (c) infection is associated with mild apoptosis throughout the juvenile brain, but NSC proliferation is unchanged; (d) the loss of NSC numbers is dependent upon the stage of NSC differentiation; and (e) immature neurons increase early during infection, concurrent with depletion of NSC pools. Collectively, we show that NSCs are exquisitely sensitive to the inflammatory microenvironment created during neuron-restricted MeV infection in juveniles, responding with an early loss of NSCs but increased neurogenesis. These studies provide insight into potential cellular mechanisms associated with long-term neurological deficits in survivors of childhood CNS infections.

Automated summary

Viral infections of the central nervous system (CNS) in children can lead to long-term neurological deficits. This study used a mouse model of measles virus infection and found that the virus caused a decrease in neural stem cell (NSC) numbers during childhood, but NSC numbers ultimately stabilized in adulthood. These findings provide insight into the potential cellular mechanisms underlying long-term neurological deficits in survivors of childhood CNS infections.