Convergent mechanisms of microglia-mediated synaptic dysfunction contribute to diverse neuropathological conditions

Changes in synaptic function are an early hallmark of neuropathological conditions that often precede symptom onset, with mounting genetic, transcriptional, and epidemiological evidence implicating microglia in this process. The correlation between infection and neurocognitive sequelae further suggests that environmental exposures modulate neuroimmune interactions and contribute to synaptic alterations. Recent studies investigating functional roles of microglia across broad neuropathological contexts including neurodegeneration, aging, neuropsychiatric and neurodevelopmental disorders, and neurotropic infections reveal convergent mechanisms underlying microglial-mediated synaptic dysfunction. We propose that early microglial changes, driven by genetic alterations coupled with environmental neuroimmune modulation, may be a common denominator that contributes to early synaptic pathologies. Here we review the evidence and discuss how microglia respond, and contribute, to synaptopathies across diverse neurological conditions, spotlighting their importance as broadly relevant therapeutic targets within neurological diseases.

Automated summary

Changes in synaptic function are early indicators of neurological disorders, and microglia play a role in this process based on genetic, transcriptional, and epidemiological evidence. Environmental exposures and infections also contribute to alterations in neuroimmune interactions and synaptic changes. Recent studies across various neurological conditions have revealed common mechanisms underlying microglial-mediated synaptic dysfunction, suggesting that early microglial alterations may be a common factor contributing to synaptic pathologies.