{"doi":"10.1016/j.ynstr.2025.100721","title":"Sex-specific regulation of microglial MyD88 in HMGB1-Induced anxiety phenotype in mice","abstract":"Stress is a significant risk factor for the development and recurrence of anxiety disorders. Stress can profoundly impact the immune system, and lead to microglial functional alterations in the medial prefrontal cortex (mPFC), a brain region involved in the pathogenesis of anxiety. High mobility group box 1 protein (HMGB1) is a potent pro-inflammatory stimulus and danger-associated molecular pattern (DAMP) released from neuronal and non-neuronal cells following stress. HMGB1 provokes pro-inflammatory responses in the brain and, when administered locally, alters behavior in the absence of other stressors. In this study, we administered dsHMGB1 into the mPFC of male and female mice for 5 days to investigate the cellular and molecular mechanisms underlying HMGB1-induced behavioral dysfunction, with a focus on cell-type specificity and potential sex differences. Here, we demonstrate that dsHMGB1 infusion into the mPFC elicited behavior changes in both sexes but only altered microglial morphology robustly in female mice. Moreover, preventing microglial changes with cell-specific ablation of the MyD88 pathway prevented anxiety-like behaviors only in females. These results support the hypothesis that microglial MyD88 signaling is a critical mediator of HMGB1-induced stress responses, particularly in adult female mice. • Infusion of HMGB1 to PFC causes behavioral changes in male and female adult mice. • Females demonstrate a more robust increase in microglial reactivity in response to HMGB1 administration. • Conditional knockout of MyD88 prevents changes in behavior and microglial reactivity in females in response to HMGB1.","journal":"Neurobiology of Stress","year":2025,"id":519264,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9527,"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":461284,"name":"Julia E. Dziabis","orcid":"0000-0002-2886-9192","position":1,"is_corresponding":false},{"id":1326849,"name":"Dang M. Nguyen","orcid":"0000-0001-6708-6265","position":2,"is_corresponding":false},{"id":814291,"name":"Dilara N. Anbarci","orcid":"0000-0003-0435-4749","position":3,"is_corresponding":false},{"id":1336001,"name":"Madeline Clark","orcid":"0000-0001-5130-5160","position":4,"is_corresponding":false},{"id":632187,"name":"Grace Zhang","orcid":"0000-0001-7322-2956","position":5,"is_corresponding":false},{"id":432897,"name":"Kafui Dzirasa","orcid":"0000-0003-4280-9994","position":6,"is_corresponding":false},{"id":310252,"name":"Staci D. Bilbo","orcid":"0000-0001-6736-7841","position":7,"is_corresponding":false},{"id":1307312,"name":"Ashleigh Rawls","orcid":"0000-0001-5261-6710","position":0,"is_corresponding":true}],"reference_count":95,"raw_metadata":null,"created_at":"2026-07-19T02:49:18.751199Z","pmid":"40236260","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":[]}