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To address this, we generated a transgenic mouse line with inducible, astrocyte-specific overexpression of the gap junction protein connexin43 (Cx43). In these mice, hippocampal astrocytes exhibited markedly elevated Cx43 protein levels and a\u2009~\u200920% increase in intercellular gap junction coupling. Enhanced coupling was accompanied by a reduction in astrocytic cell volume and branching, without affecting passive membrane properties or astrocyte density in the hippocampus. Cx43 overexpression had no detectable impact on adult neurogenesis in the dentate gyrus, nor did it alter hippocampal synaptic efficacy or plasticity. Notably, in a mouse model of temporal lobe epilepsy with hippocampal sclerosis, astrocytic Cx43 overexpression attenuated chronic epileptic activity and the extent of sclerosis, supporting an antiepileptic role of the astroglial network. Collectively, these findings enhance our understanding of the functional relevance of astrocytic gap junction coupling in health and disease, with potential implications for the design of new treatment strategies.<\/jats:p>","DOI":"10.1007\/s11064-025-04558-w","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T08:51:21Z","timestamp":1758185481000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Induced Overexpression of Connexin43 in Astrocytes Attenuates the Progression of Experimental Temporal Lobe Epilepsy"],"prefix":"10.1007","volume":"50","author":[{"given":"Oussama","family":"Kherbouche","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas","family":"Henning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pia","family":"Niemann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Geisen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerald","family":"Seifert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Henneberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd K.","family":"Fleischmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2579-8357","authenticated-orcid":false,"given":"Christian","family":"Steinh\u00e4user","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0090-7553","authenticated-orcid":false,"given":"Peter","family":"Bedner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"4558_CR1","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/nrn2757","volume":"11","author":"C Giaume","year":"2010","unstructured":"Giaume C, Koulakoff A, Roux L et al (2010) Astroglial networks: a step further in neuroglial and gliovascular interactions. 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Experiments were approved by the North Rhine\u2013Westphalia State Agency for Nature, Environment and Consumer Protection (approval number 81-02.04.2020.A420).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}],"article-number":"303"}}