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

Annals of the New York Academy of Sciences
Authors
Keywords
Abstract

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.

Year of Publication
2023
Journal
Annals of the New York Academy of Sciences
Date Published
06/2023
ISSN
1749-6632
DOI
10.1111/nyas.15010
PubMed ID
37272510
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