To summarize current evidence on microglial biology related to autism spectrum disorder (ASD), focusing on heterogeneity, immunometabolic regulation, and synapse-related pathways, and their implications for understanding ASD mechanisms.
Key Findings:
Microglial involvement in ASD is heterogeneous and context-dependent, varying by region, developmental stage, and sex, which has implications for treatment strategies.
Evidence does not support a single ASD-wide microglial phenotype but indicates specific immune- and glia-associated alterations in subsets of ASD brains, suggesting targeted interventions may be necessary.
Microglial functions such as lipid handling, mitochondrial function, and synaptic remodeling are critical in understanding their role in ASD and potential therapeutic avenues.
Interpretation:
The literature suggests a need for precise interpretations of microglial biology in ASD, emphasizing developmental timing and cellular context over non-specific inflammatory labels, which may inform future research directions.
Limitations:
Most human ASD evidence is cross-sectional and postmortem, limiting longitudinal insights and the ability to track changes over time.
In vivo imaging provides glia-associated signals rather than specific microglial signals, complicating the interpretation of results.
Effect modifiers such as developmental stage, sex, and comorbidities are often unevenly represented, which may skew findings and their applicability.
Conclusion:
A nuanced understanding of microglial roles in ASD is essential, focusing on specific mechanisms rather than broad inflammatory responses, to inform potential therapeutic targets.
