{"doi":"10.1101/2025.04.28.651094","title":"Maternal Immune Activation Disrupts Epigenomic and Functional Maturation of Cortical Excitatory Neurons","abstract":"Elevated levels of maternal pro-inflammatory cytokines during gestation can disrupt offspring neural development, increasing the risk of neurodevelopmental disorders. We studied the effects of Poly(I:C)-induced maternal immune activation (PIC-MIA) during mid-gestation on developing cortical excitatory neurons' DNA methylation and transcriptome. PIC-MIA disrupted the developmental regulation of synapse-related genes and of genes implicated in autism spectrum disorders. Genomic regions that gain or lose DNA methylation during normal development were altered following PIC-MIA, including neurodevelopmental transcription factor binding sites. The DNA methylation and transcriptional changes were consistent with a delay in excitatory neuron maturation. Whole-cell recordings showed that PIC-MIA preferentially altered the physiological development of layer 5 excitatory neurons. Taken together, present results suggest that alterations in the epigenome, through the disruption of circuit formation, may drive the long-term consequences of maternal infection during gestation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":565077,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"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":750639,"name":"Jessica Arzavala","orcid":null,"position":1,"is_corresponding":false},{"id":1468634,"name":"Adoni Duarte","orcid":null,"position":2,"is_corresponding":false},{"id":486494,"name":"Shiyuan Wang","orcid":"0000-0002-5028-5839","position":3,"is_corresponding":false},{"id":484608,"name":"Junhao Li","orcid":"0000-0001-6784-3780","position":4,"is_corresponding":false},{"id":553409,"name":"Hanqing Liu","orcid":"0000-0002-5114-6048","position":5,"is_corresponding":false},{"id":38352,"name":"Julia K. Osteen","orcid":"0000-0001-7058-3297","position":6,"is_corresponding":false},{"id":37784,"name":"Rosa G. Castanon","orcid":"0000-0003-1791-002X","position":7,"is_corresponding":false},{"id":3788,"name":"Joseph R. Nery","orcid":"0000-0003-0153-5659","position":8,"is_corresponding":false},{"id":503407,"name":"Susan B. Powell","orcid":"0000-0002-7474-9300","position":9,"is_corresponding":false},{"id":3799,"name":"Joseph R. Ecker","orcid":"0000-0001-5799-5895","position":10,"is_corresponding":false},{"id":21452,"name":"Eran A. Mukamel","orcid":"0000-0003-3203-9535","position":11,"is_corresponding":false},{"id":38373,"name":"M. Margarita Behrens","orcid":"0000-0002-7168-8186","position":12,"is_corresponding":false},{"id":1468234,"name":"Chi-Yu Lai","orcid":"0000-0002-5498-1946","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:56:24.872312Z","pmid":"42255505","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":[]}