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Neuroligin 2 (NL2) is a postsynaptic cell\u2010adhesion protein involved in the formation of inhibitory synapses. Since epileptic seizures are attributed to excessive brain neuronal activity, we hypothesized that NL2\u2010mediated inhibitory signaling suppresses seizures. Male C57BL\/6J mice were bilaterally injected into the hippocampus (HPC) with an adeno\u2010associated virus (AAV) vector expressing NL2 under the control of synapsin I promoter (AAV\u2010NL2). Mice treated with AAV\u2010NL2 were intraperitoneally administered with 35 mg\/kg pentylenetetrazol (PTZ) every other day. Ordinal logistic regression analysis revealed that NL2 expression exerted a protective effect against seizure progression induced by repeated PTZ administration. In addition, ventral HPC c\u2010Fos protein levels were significantly suppressed with AAV\u2010NL2 injection. NL2 expression induced by intra\u2010HPC AAV\u2010NL2 injection attenuates the progression of PTZ\u2010induced seizures and may represent a potential target for seizure control.<\/jats:p>","DOI":"10.1002\/jgm.70116","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T06:17:23Z","timestamp":1791440243000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adeno\u2010Associated Virus Vector\u2010Mediated Expression of Neuroligin 2 in the Mouse Hippocampus Attenuates the Progression of Pentylenetetrazol\u2010Induced Seizures"],"prefix":"10.1002","volume":"28","author":[{"given":"Tomohiro","family":"Tokutake","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Therapy &amp; Neuropharmacology, Faculty of Pharmaceutical Sciences University of Toyama  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2483-6489","authenticated-orcid":false,"given":"Akane","family":"Hara","sequence":"additional","affiliation":[{"name":"Laboratory of Mathematical Medicine and Pharmaceutical Assessment, Faculty of Pharmaceutical Sciences University of Toyama  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayano","family":"Murayama","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Therapy &amp; Neuropharmacology, Faculty of Pharmaceutical Sciences University of Toyama  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuto","family":"Mitsuda","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Therapy &amp; Neuropharmacology, Faculty of Pharmaceutical Sciences University of Toyama  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1953-9378","authenticated-orcid":false,"given":"Jun","family":"Yokose","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Therapy &amp; Neuropharmacology, Faculty of Pharmaceutical Sciences University of Toyama  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1231-0649","authenticated-orcid":false,"given":"Yusuke","family":"Yano","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Therapy &amp; Neuropharmacology, Faculty of Pharmaceutical Sciences University of Toyama  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7033-5357","authenticated-orcid":false,"given":"Yuki","family":"Shigetsura","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Ito","sequence":"additional","affiliation":[{"name":"Division of Neurological Gene Therapy, Center for Open Innovation Jichi Medical University  Shimotsuke Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Takino","sequence":"additional","affiliation":[{"name":"Division of Neurological Gene Therapy, Center for Open Innovation Jichi Medical University  Shimotsuke Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Kumagai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Jichi Medical University  Shimotsuke Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuniko","family":"Shimazaki","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Jichi Medical University  Shimotsuke Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3185-7790","authenticated-orcid":false,"given":"Shin\u2010Ichi","family":"Muramatsu","sequence":"additional","affiliation":[{"name":"Division of Neurological Gene Therapy, Center for Open Innovation Jichi Medical University  Shimotsuke Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6916-9160","authenticated-orcid":false,"given":"Atsumi","family":"Nitta","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Therapy &amp; Neuropharmacology, Faculty of Pharmaceutical Sciences University of Toyama  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1111\/j.0013-9580.2005.66104.x","article-title":"Epileptic Seizures and Epilepsy: Definitions Proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)","volume":"46","author":"Fisher R. 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