Complement and microglia activation mediate stress-induced synapse loss in layer 2/3 of the medial prefrontal cortex in male mice.

ABSTRACT: Spatially heterogeneous synapse loss is a characteristic of many psychiatric and neurological disorders, but the underlying mechanisms are unclear. Here, we show that spatially-restricted complement activation mediates stress-induced heterogeneous microglia activation and synapse loss localized to the upper layers of the medial prefrontal cortex (mPFC) in male mice. Single cell RNA sequencing also reveals a stress-associated microglia state marked by high expression of the apolipoprotein E gene (Apoe^high) localized to the upper layers of the mPFC. Mice lacking complement component C3 are protected from stress-induced layer-specific synapse loss, and the Apoe^high microglia population is markedly reduced in the mPFC of these mice. Furthermore, C3 knockout mice are also

SUBMITTER: Tillmon H 

PROVIDER: S-EPMC11557709 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature