{"doi":"10.1101/2022.11.03.511881","title":"Astrocytes regulate spatial memory in a sex-specific manner","abstract":"Abstract Cognitive processes and neurocognitive disorders are regulated by astrocytes and have prominent sex differences. However, the contribution of astrocytes to sex differences is not known. We leveraged astrocyte-targeted gene editing and chemogenetics in adult mice to reveal that astrocytic glutamate receptors and other G protein-coupled receptors (GPCRs) modulate hippocampus-dependent cognitive function in a sexually dimorphic manner. In females, spatial memory was improved by increasing metabotropic glutamate receptor 3 (mGluR3) in astrocytes or stimulating astrocytic G i/o -coupled signaling, whereas stimulating G s -coupled signaling impaired memory. However, in males, memory was improved by reducing mGluR3 or stimulating G s -coupled signaling, whereas stimulating G i/o -coupled signaling impaired memory. Thus, memory requires a sex-specific balance of astrocytic G s -coupled and G i/o -coupled receptor activities, and disease-associated alterations or therapeutic targeting of these pathways may cause opposing sex-dependent effects on cognitive function. Summary Glia cause sex-specific changes in cognition","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":302124,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":989277,"name":"Fernando Palaguachi","orcid":"0000-0001-5403-7093","position":1,"is_corresponding":false},{"id":989828,"name":"Avital Licht-Murava","orcid":null,"position":2,"is_corresponding":false},{"id":816441,"name":"Daniel Barnett","orcid":"0000-0002-1340-4413","position":3,"is_corresponding":false},{"id":708566,"name":"Till S. Zimmer","orcid":"0000-0002-6869-3697","position":4,"is_corresponding":false},{"id":989278,"name":"Constance Zhou","orcid":"0000-0002-8528-1862","position":5,"is_corresponding":false},{"id":278345,"name":"Samantha R. McDonough","orcid":"0000-0001-5263-3107","position":6,"is_corresponding":false},{"id":989279,"name":"Adam L. Orr","orcid":"0000-0003-0338-7709","position":7,"is_corresponding":false},{"id":217801,"name":"Adam L. Orr","orcid":null,"position":8,"is_corresponding":false},{"id":846741,"name":"Anna G. Orr","orcid":"0000-0002-4036-4277","position":9,"is_corresponding":false},{"id":989276,"name":"Samantha M. Meadows","orcid":"0000-0002-0954-5379","position":0,"is_corresponding":true}],"reference_count":90,"raw_metadata":null,"created_at":"2026-07-19T00:32:06.309890Z","pmid":null,"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":[]}