{"doi":"10.1093/pnasnexus/pgaf146","title":"Astrocyte <i>Fabp7</i> modulates nocturnal seizure threshold and activity-dependent gene expression in mouse brain","abstract":"Abstract Epileptic seizures often track with time of day and/or changes in vigilance state; however, specific molecular and cellular mechanisms driving the ictal and temporal associations are lacking. Astrocytes are a type of glial cell known to modulate neuronal excitability and circadian rhythms. These cells also abundantly express fatty acid–binding protein 7 (Fabp7), a clock-driven molecule necessary for normal sleep regulation, lipid signaling, and gene transcription. To determine whether Fabp7 influences time-of-day-dependent seizure susceptibility, we tested male C57/BL6N wild-type (WT) and Fabp7 knockout (KO) mice using electroshock seizure threshold. Compared with WT mice, Fabp7 KO mice exhibited markedly higher general- and maximal-electroshock seizure thresholds (GESTs and MESTs, respectively) during the dark phase, but not the light phase. We used RNA-seq to determine the role of Fabp7 in activity-dependent gene expression in nocturnal seizures and compared genome-wide mRNA expression in cortical/hippocampal tissue collected from WT-MEST and Fabp7 KO-MEST mice with WT-SHAM and Fabp7 KO-SHAM mice during the dark period. Whereas significant differential expression of immediate early genes was observed in WT-MEST compared with WT-SHAM, this effect was blocked in the Fabp7 KO-MEST versus Fabp7 KO-SHAM. Gene ontology and pathway analysis of all groups revealed significant overlap between WT-MEST:WT-SHAM and Fabp7 KO-SHAM:WT-SHAM comparisons, suggesting basal mRNA levels of core molecular and cellular mechanisms in the brain of Fabp7 KO approximate postictal WT brain. Together, these data suggest that Fabp7 regulates time-of-day-dependent neural excitability and that neural activity likely interacts with astrocyte Fabp7-mediated signaling cascades to influence activity-dependent gene expression.","journal":"PNAS Nexus","year":2025,"id":532343,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"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":0.9517,"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":728654,"name":"Carlos C. Flores","orcid":"0000-0003-3771-0906","position":1,"is_corresponding":false},{"id":700202,"name":"Yuji Owada","orcid":"0000-0002-5109-0531","position":2,"is_corresponding":false},{"id":795169,"name":"Christopher J. Davis","orcid":"0000-0002-9613-928X","position":3,"is_corresponding":false},{"id":318660,"name":"Thomas N. Ferraro","orcid":"0000-0003-2250-8772","position":4,"is_corresponding":false},{"id":628386,"name":"Yool Lee","orcid":"0000-0003-0498-3342","position":5,"is_corresponding":false},{"id":1413525,"name":"Wheaton L. Schroeder","orcid":"0000-0003-2302-1237","position":6,"is_corresponding":false},{"id":339511,"name":"Jason R. Gerstner","orcid":"0000-0003-3113-6974","position":7,"is_corresponding":false},{"id":937152,"name":"Micah Lefton","orcid":"0000-0001-7220-8861","position":0,"is_corresponding":true}],"reference_count":15,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:51:23.237536Z","pmid":"40386682","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":[]}