{"doi":"10.1038/s41380-025-03097-8","title":"Opposing roles of microglial and macrophagic C3ar1 signaling in stress-induced synaptic and behavioral changes","abstract":"The social deficits following chronic stress conditions are linked to synaptic dysfunction in the brain. Complement system plays a critical role in synapse regulation. Although complement has been implicated in chronic stress-induced behavior deficits the cellular substrates and mechanisms underlying complement-mediated behavior changes under chronic stress conditions are not known. In the present study, we investigated the role of complement component 3a receptor (C3ar1) in microglia and monocytes/macrophages (Mo/MΦ) in chronic unpredictable stress (CUS)-induced synapse loss and behavior deficits in mice. We found that deletion of microglial C3ar1 attenuated stress-induced social behavior deficits and changes in neuroinflammatory as well as synaptic markers in the prefrontal cortex (PFC). RNA sequencing data revealed that microglial C3ar1 deletion attenuates CUS-mediated changes in the expression of immediate-early genes such as Fos and Nuclear Receptor Subfamily 4 Group A Member 1 (Nr4a1) in the PFC. In contrast, lack of C3ar1 in Mo/MΦ induced social behavior deficits. Together, these findings indicate opposite functions of C3ar1 signaling in microglia and Mo/MΦ under chronic stress conditions.","journal":"Molecular Psychiatry","year":2025,"id":526221,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9498,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1385440,"name":"Alona Bartosh","orcid":null,"position":1,"is_corresponding":false},{"id":1012135,"name":"Dania Jose","orcid":null,"position":2,"is_corresponding":false},{"id":1402284,"name":"Jocelyn Mata","orcid":null,"position":3,"is_corresponding":false},{"id":1213141,"name":"Usama Khamis Hussein","orcid":"0000-0002-7325-3004","position":4,"is_corresponding":false},{"id":381782,"name":"Fernanda Laezza","orcid":"0000-0003-1141-1852","position":5,"is_corresponding":false},{"id":13182,"name":"Zhongming Zhao","orcid":"0000-0002-3477-0914","position":6,"is_corresponding":false},{"id":433927,"name":"Anilkumar Pillai","orcid":"0000-0002-1952-8556","position":7,"is_corresponding":false},{"id":311697,"name":"Ashutosh Tripathi","orcid":"0000-0003-0904-0650","position":0,"is_corresponding":true}],"reference_count":131,"raw_metadata":null,"created_at":"2026-07-19T02:50:30.402772Z","pmid":"40640554","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":[]}