Abnormal behaviors in individuals with neurodevelopmental disorders are generally believed to be irreversible. Here, we show that voluntary wheel running ameliorates the abnormalities in sociability, repetitiveness, and anxiety observed in a mouse model of a neurodevelopmental disorder induced by maternal immune activation (MIA). Exercise activates a portion of dentate granule cells, normalizing the density of hippocampal CA3 synapses, which is excessive in the MIA-affected offspring. The synaptic surplus in the MIA offspring is induced by deficits in synapse engulfment by microglia, which is normalized by exercise through microglial activation. Finally, chemogenetically induced activation of granule cells promotes the engulfment of CA3 synapses. Thus, our study proposes a role of voluntary exercise in the modulation of behavioral and synaptic abnormalities in neurodevelopmental disorders.
Keywords: autism; exercise; hippocampus; maternal immune activation; microglia; synapse.
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