{"doi":"10.3390/cells12121669","title":"Role of Impaired Astrocyte Gap Junction Coupling in Epileptogenesis","abstract":"<jats:p>The gap-junction-coupled astroglial network plays a central role in the regulation of neuronal activity and synchronisation, but its involvement in the pathogenesis of neuronal diseases is not yet understood. Here, we present the current state of knowledge about the impact of impaired glial coupling in the development and progression of epilepsy and discuss whether astrocytes represent alternative therapeutic targets. We focus mainly on temporal lobe epilepsy (TLE), which is the most common form of epilepsy in adults and is characterised by high therapy resistance. Functional data from TLE patients and corresponding experimental models point to a complete loss of astrocytic coupling, but preservation of the gap junction forming proteins connexin43 and connexin30 in hippocampal sclerosis. Several studies further indicate that astrocyte uncoupling is a causal event in the initiation of TLE, as it occurs very early in epileptogenesis, clearly preceding dysfunctional changes in neurons. However, more research is needed to fully understand the role of gap junction channels in epilepsy and to develop safe and effective therapeutic strategies targeting astrocytes.</jats:p>","journal":"Cells","year":2023,"id":610705,"datarank":0.49983067652628066,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":0.0,"self_endowment_contribution":0.49983067652628066,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"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":614260,"name":"Christian Steinhäuser","orcid":"0000-0003-2579-8357","position":1,"is_corresponding":false},{"id":841651,"name":"Peter Bedner","orcid":"0000-0003-0090-7553","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Role of Impaired Astrocyte Gap Junction Coupling in Epileptogenesis","abstract":"<jats:p>The gap-junction-coupled astroglial network plays a central role in the regulation of neuronal activity and synchronisation, but its involvement in the pathogenesis of neuronal diseases is not yet understood. Here, we present the current state of knowledge about the impact of impaired glial coupling in the development and progression of epilepsy and discuss whether astrocytes represent alternative therapeutic targets. We focus mainly on temporal lobe epilepsy (TLE), which is the most common form of epilepsy in adults and is characterised by high therapy resistance. Functional data from TLE patients and corresponding experimental models point to a complete loss of astrocytic coupling, but preservation of the gap junction forming proteins connexin43 and connexin30 in hippocampal sclerosis. Several studies further indicate that astrocyte uncoupling is a causal event in the initiation of TLE, as it occurs very early in epileptogenesis, clearly preceding dysfunctional changes in neurons. However, more research is needed to fully understand the role of gap junction channels in epilepsy and to develop safe and effective therapeutic strategies targeting astrocytes.</jats:p>","is_dataset_classified":null,"base_score":3.332204510175204,"endowment":3.332204510175204,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37371139","pmcid":"PMC10297487","openalex_id":"https://openalex.org/W4381662618","authors":[],"funders":[{"funder_name":"BMBF","grant_id":"01DN20001","title":null},{"funder_name":"BMBF","grant_id":"16GW0182","title":null},{"funder_name":"BMBF","grant_id":"H2020 MSCA-ITN","title":null},{"funder_name":"European Commission","grant_id":"722053","title":"Training, Research and Raising of Public Awareness in Cell Biology and Pathology of Neuroglia"}],"total_grants":4,"fwci":2.4342,"citation_percentile":0.90048193,"influential_citations":0,"citation_trend":[{"year":2022,"count":1},{"year":2023,"count":4},{"year":2024,"count":12},{"year":2025,"count":8},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2073-4409/12/12/1669/pdf?version=1687250713","host_type":"journal"},{"url":"https://www.mdpi.com/2073-4409/12/12/1669/pdf?version=1687250713","host_type":"publisher"},{"url":"https://www.mdpi.com/2073-4409/12/12/1669/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/cells12121669","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37371139","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10297487","host_type":"repository"},{"url":"https://doaj.org/article/2893151a1b7a483c90aecf5c25208966","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/cells12121669","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10297487/pdf/cells-12-01669.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10297487","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10297487?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.20944/preprints202301.0531.v1","host_type":""},{"url":"http://dx.doi.org/10.3390/cells12121669","host_type":""}],"fields_of_study":["Connexins and lens biology","Neuroscience and Neuropharmacology Research","Ion channel regulation and function","03 medical and health sciences","0302 clinical medicine","Humans","Astrocytes","Gap Junctions","Epilepsy, Temporal Lobe","Epilepsy","Connexins"],"mesh_terms":["Astrocytes","Epilepsy","Epilepsy, Temporal Lobe","Humans","Gap Junctions","Connexins"],"keywords":["Epileptogenesis","Neuroscience","Epilepsy","Gap junction","Astrocyte","Hippocampal sclerosis","Hippocampus","Temporal lobe","Medicine","Psychology","Biology","Central nervous system","Cell biology","Temporal lobe epilepsy","connexin 43","Gap Junction Coupling","Connexin 30","QH573-671","Biochemistry and Molecular Biology","Biology and Life Sciences","Gap Junctions","Review","Connexins","Epilepsy, Temporal Lobe","Astrocytes","Humans","Cytology"],"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":"2026-08-01T10:42:07.833499Z","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":[]}