Cerebellar Neuroinflammation Modulates Social Behavior in Mice

Sociability is a complex behavior involving distributed neural circuits, including the cerebellum. Increasing evidence suggests that cerebellar dysfunction may contribute to the behavioral alterations observed in autism spectrum disorder (ASD), although the underlying mechanisms remain poorly understood. Here, we investigated whether cerebellar neuroinflammation contributes to alterations in social behavior. Using the prenatal valproic acid (VPA) mouse model of ASD, we found reduced sociability in male offspring, accompanied by transient alterations in Purkinje cell density during postnatal development that were not maintained into adulthood. To directly assess the contribution of inflammation, we induced neuroinflammation in lobules VI/VII of the cerebellum in adult male mice. This manipulation produced a marked reduction in sociability, without alterations in Purkinje cell density. Systemic treatment with dexamethasone completely prevented the behavioral deficit, whereas ibuprofen produced a partial effect. Dexamethasone treatment was also associated with reduced microglial activation. Together, these findings support a role for cerebellar neuroinflammation in the regulation of social behavior and suggest that microglial activation may contribute to inflammation-induced sociability deficits.