{"doi":"10.1016/j.neuint.2022.105383","title":"Opposing reduced VPAC1 and enhanced VPAC2 VIP receptors in the hippocampus of the Li2+-pilocarpine rat model of temporal lobe epilepsy","abstract":null,"journal":"Neurochemistry International","year":2022,"id":614595,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1583793,"name":"Marta Bento","orcid":null,"position":1,"is_corresponding":false},{"id":1583794,"name":"Ana Caulino-Rocha","orcid":null,"position":2,"is_corresponding":false},{"id":1583795,"name":"Seweryn Pawlak","orcid":null,"position":3,"is_corresponding":false},{"id":1583796,"name":"Diana Cunha-Reis","orcid":"0000-0002-0900-9306","position":4,"is_corresponding":false},{"id":1583792,"name":"André Serpa","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Opposing reduced VPAC1 and enhanced VPAC2 VIP receptors in the hippocampus of the Li2+-pilocarpine rat model of temporal lobe epilepsy","abstract":"VIP binding sites are upregulated in mesial temporal lobe epilepsy (MTLE) patients, also suffering from severe cognitive deficits. Although altered VIP and VIP receptor levels were described in rodent models of epilepsy, the VIP receptor subtype(s) were never identified. We now investigated how VPAC<sub>1</sub> and VPAC<sub>2</sub> receptor levels change in the Li<sup>2+</sup>-pilocarpine rat model of MTLE. Cognitive decline and altered synaptic plasticity as estimated from phosphorylation of AMPA GluA1 subunit on Ser831 and Ser845 and AMPA GluA1/GluA2 ratio was also probed. Animals showing spontaneous recurrent seizures (SRSs) for at least 4 weeks showed impaired learning in the radial arm maze (RAM) and presented decreased VPAC<sub>1</sub> and increased VPAC<sub>2</sub> receptor levels. In addition, SRSs rats showed increased AMPA GluA1 phosphorylation in Ser831 and Ser845, marked decrease in GluA1 levels and a milder decrease in GluA2 levels. Consequently, the GluA1/GluA2 ratio was also decreased in SRSs rats. Altered VIP receptor levels may differentially prevent or contribute to MTLE pathology, since VPAC<sub>1</sub> receptors promote the endogenous control of LTP, mediate endogenous VIP neuroprotection against altered synaptic plasticity following epileptiform activity, and mediate anti-inflammatory actions in microglia, while VPAC<sub>2</sub> receptors mediate VIP endogenous neuroprotection against neonatal excitotoxicity and prevent reactive astrogliosis. This discovery imposes a different mindset for considering VIP receptors as therapeutic targets in MTLE, allowing a differential targeting of the cellular events contributing to epileptogenesis.","is_dataset_classified":null,"base_score":2.302585092994046,"endowment":2.302585092994046,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35787395","pmcid":null,"openalex_id":"https://openalex.org/W4283795634","authors":[],"funders":[{"funder_name":"Fundação para a Ciência e a Tecnologia","grant_id":"SFRH/BPD/81358/2011","title":"EVALUATING THERAPEUTIC OPPORTUNITIES FOR PREVENTING EPILEPTOGENESIS, COGNITIVE DECLINE AND SUDDEN DEATH IN EPILEPSY"},{"funder_name":"Fundação para a Ciência e a Tecnologia","grant_id":"UIDP/04046/2020","title":"Biosystems and Integrative Sciences Institute"},{"funder_name":"Fundação para a Ciência e a Tecnologia","grant_id":"UIDB/04046/2020","title":"Biosystems and Integrative Sciences Institute"},{"funder_name":"Fundação para a Ciência e a Tecnologia","grant_id":"PTDC/SAU- NEU /103,639/2008","title":null}],"total_grants":4,"fwci":0.8278,"citation_percentile":0.66186687,"influential_citations":0,"citation_trend":[{"year":2022,"count":1},{"year":2023,"count":3},{"year":2024,"count":3},{"year":2025,"count":2}],"oa_status":"closed","license":"Elsevier TDM","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0197018622001085?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0197018622001085?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.neuint.2022.105383","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35787395","host_type":"repository"}],"fields_of_study":["Neuropeptides and Animal Physiology","Pharmacological Effects and Toxicity Studies","Epilepsy research and treatment","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Animals","Epilepsy, Temporal Lobe","Hippocampus","Pilocarpine","Seizures","Receptors, Vasoactive Intestinal Peptide","alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid","Rats"],"keywords":["Epileptogenesis","AMPA receptor","Neuroscience","Astrogliosis","Neuroprotection","Hippocampal formation","Hippocampus","Pilocarpine","Receptor","Synaptic plasticity","Epilepsy","Glutamate receptor","Biology","Psychology","Internal medicine","Medicine","Central nervous system","VIP","Learning and memory","Vpac(1) Receptors","Vpac(2) Receptors","Epilepsy, Temporal Lobe","Seizures","Animals","Receptors, Vasoactive Intestinal Peptide","alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid","Rats"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T14:37:20.410505Z","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":[]}