Microglia, cerebellar inflammation, and autism spectrum disorders: Developmental mechanisms and therapeutic perspectives

Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by deficits in social interaction and communication, as well as restricted and repetitive behaviors. These conditions often co-occur with medical issues linked to synaptic alterations, which compromise synaptic integrity and are associated with brain circuit dysfunction. Both human and animal studies have identified cerebellar structural and functional alterations in subsets of ASD cases, with evidence of abnormal morphology and disrupted connectivity correlating with symptom severity. Numerous studies further suggest that neuroinflammation and microglia dysfunction may contribute to atypical cerebellar development during critical postnatal windows and may be associated with ASD-like phenotypes. However, the timing and mechanisms underlying the onset of these processes remain unclear, and a primary causal role in human ASD has not been established. This review synthesizes current knowledge on microglia in early stages of cerebellar development and discusses how cerebellar inflammation could be linked to ASD-related phenotypes. A better understanding of these pathological processes and their behavioral correlates may reveal opportunities for early-life intervention strategies.