GEO series

Complement and microglia activation mediates stress-induced synapse loss in layer 2/3 of the medial prefrontal cortex

GSE272813 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2024/09/09 Platform GPL24247

Summary

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 mouse medial prefrontal cortex (mPFC). Single cell RNA sequencing also reveals a stress-associated microglia state marked by high expression of the apolipoprotein E gene (Apoehigh) localized to the upper layers of the mPFC. Mice lacking complement component C3 are protected from stress-induced layer-specific synapse loss, and the Apoehigh microglia population is markedly reduced in the mPFC of these mice. Furthermore, C3 knockout mice are also resilient to stress-induced anhedonia and working memory behavioral deficits. Our findings suggest that region-specific complement and microglia activation can contribute to the disease-specific spatially restricted patterns of synapse loss and clinical symptoms found in many brain diseases.

Published in

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

Tillmon H, Soteros BM, Shen L et al. · Nature communications 2024 · PMID 39532876 · doi:10.1038/s41467-024-54007-5

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Also filed as BioProject PRJNA1138783 and SRA study SRP521450. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39532876) ↗

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