{"doi":"10.1038/s41467-024-54007-5","title":"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 (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. Synapse loss is central to the pathogenesis of stress-related disorders. Here, the authors show that targeted synapse removal by microglia and complement during stress contributes to the effects of stress on behavior.","journal":"Nature Communications","year":2024,"id":419679,"datarank":0.6702867059084131,"base_score":3.6888794541139363,"endowment":3.6888794541139363,"self_citation_contribution":0.5533319181170905,"citation_network_contribution":0.11695478779132264,"self_endowment_contribution":0.5533319181170905,"citer_contribution":0.11695478779132264,"corpus_percentile":null,"corpus_rank":null,"citation_count":39,"citer_count":37,"citers_with_citation_signal":14,"citers_with_endowment":14,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9625,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE272813"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1176298,"name":"Breeanne M. Soteros","orcid":"0000-0002-4714-5165","position":1,"is_corresponding":false},{"id":160520,"name":"Liang Shen","orcid":null,"position":2,"is_corresponding":false},{"id":1209726,"name":"Qifei Cong","orcid":"0000-0002-4446-7222","position":3,"is_corresponding":false},{"id":959980,"name":"Mackenna Wollet","orcid":null,"position":4,"is_corresponding":false},{"id":1176651,"name":"Julianne General","orcid":null,"position":5,"is_corresponding":false},{"id":1176652,"name":"Hanna Chin","orcid":null,"position":6,"is_corresponding":false},{"id":1176653,"name":"John Beichen Lee","orcid":null,"position":7,"is_corresponding":false},{"id":891041,"name":"Flavia Carreño","orcid":null,"position":8,"is_corresponding":false},{"id":588757,"name":"David A. Morilak","orcid":"0000-0001-6689-6258","position":9,"is_corresponding":false},{"id":498738,"name":"Jun Hee Kim","orcid":"0000-0003-0207-8410","position":10,"is_corresponding":false},{"id":1176299,"name":"Gek-Ming Sia","orcid":"0000-0001-9333-0065","position":11,"is_corresponding":false},{"id":730716,"name":"Haven Tillmon","orcid":null,"position":0,"is_corresponding":true}],"reference_count":123,"raw_metadata":null,"created_at":"2026-07-19T01:57:19.937291Z","pmid":"39532876","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}