{"doi":"10.3390/ijms24010508","title":"Dysregulation of ErbB4 Signaling Pathway in the Dorsal Hippocampus after Neonatal Hypoxia-Ischemia and Late Deficits in PV+ Interneurons, Synaptic Plasticity and Working Memory","abstract":"Neonatal hypoxic-ischemic (HI) injury leads to deficits in hippocampal parvalbumin (PV)+ interneurons (INs) and working memory. Therapeutic hypothermia (TH) does not prevent these deficits. ErbB4 supports maturation and maintenance of PV+ IN. Thus, we hypothesized that neonatal HI leads to persistent deficits in PV+ INs, working memory and synaptic plasticity associated with ErbB4 dysregulation despite TH. P10 HI-injured mice were randomized to normothermia (NT, 36 °C) or TH (31 °C) for 4 h and compared to sham. Hippocampi were studied for α-fodrin, glial fibrillary acidic protein (GFAP), and neuroregulin (Nrg) 1 levels; erb-b2 receptor tyrosine kinase 4 (ErbB4)/ Ak strain transforming (Akt) activation; and PV, synaptotagmin (Syt) 2, vesicular-glutamate transporter (VGlut) 2, Nrg1, and ErbB4 expression in coronal sections. Extracellular field potentials and behavioral testing were performed. At P40, deficits in PV+ INs correlated with impaired memory and coincided with blunted long-term depression (LTD), heightened long-term potentiation (LTP) and increased Vglut2/Syt2 ratio, supporting excitatory-inhibitory (E/I) imbalance. Hippocampal Nrg1 levels were increased in the hippocampus 24 h after neonatal HI, delaying the decline documented in shams. Paradoxically ErbB4 activation decreased 24 h and again 30 days after HI. Neonatal HI leads to persistent deficits in hippocampal PV+ INs, memory, and synaptic plasticity. While acute decreased ErbB4 activation supports impaired maturation and survival after HI, late deficit reemergence may impair PV+ INs maintenance after HI.","journal":"International Journal of Molecular Sciences","year":2022,"id":264783,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"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":922903,"name":"Pritika Parmar","orcid":"0000-0003-2549-699X","position":1,"is_corresponding":false},{"id":596020,"name":"Sarah C. Miller","orcid":"0000-0003-3470-8798","position":2,"is_corresponding":false},{"id":923335,"name":"Paul Emerson","orcid":null,"position":3,"is_corresponding":false},{"id":430743,"name":"Charles Lechner","orcid":"0000-0003-4695-7644","position":4,"is_corresponding":false},{"id":430744,"name":"M Pierre","orcid":"0009-0009-3714-0545","position":5,"is_corresponding":false},{"id":922904,"name":"Neetika Rastogi","orcid":"0000-0001-7223-1463","position":6,"is_corresponding":false},{"id":922905,"name":"Michael Nugent","orcid":"0000-0002-2685-2426","position":7,"is_corresponding":false},{"id":922906,"name":"Sarah Ann Duck","orcid":"0000-0002-3362-6021","position":8,"is_corresponding":false},{"id":386166,"name":"Alfredo Kirkwood","orcid":"0000-0001-9148-9742","position":9,"is_corresponding":false},{"id":430745,"name":"Raul Chavez‐Valdez","orcid":"0000-0002-0788-8028","position":10,"is_corresponding":false},{"id":719722,"name":"Harisa Spahic","orcid":"0000-0002-1968-4073","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-19T00:26:41.845195Z","pmid":"36613949","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":[]}