{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:19:23Z","timestamp":1791479963946,"version":"4.3.4"},"reference-count":55,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T00:00:00Z","timestamp":1641168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Despite the increasing availability of effective drugs, around one\u2010third of patients with epilepsy are still resistant to pharmacotherapy. Gene therapy has been suggested as a plausible approach to achieve seizure control, in particular for patients with focal epilepsy. Because seizures develop across wide spans of the brain in many forms of epilepsy, global delivery of the vectors is necessary to tackle such generalized seizures. Neuroligin 2 (<jats:italic>NL2<\/jats:italic>) is a postsynaptic cell adhesion molecule that induces or strengthens inhibitory synaptic function by specifically combining with neurexin 1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In the present study, we applied an adeno\u2010associated virus (AAV) type 9 vector expressing <jats:italic>NL2<\/jats:italic> to modulate neuronal excitability in broad areas of the brain in epileptic (EL) mice, a model of polygene epilepsy. We administered the AAV vector expressing Flag\u2010tagged <jats:italic>NL2<\/jats:italic> under the synapsin I promoter (AAV\u2010NL2) via cardiac injection 6\u2009weeks after birth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significant reductions in the duration, strength and frequency of seizure were observed during a 14\u2010week observation period in NL2\u2010treated EL mice compared to untreated or AAV\u2010green fluorescent protein\u2010treated EL mice. No behavioral abnormality was observed in NL2\u2010treated EL mice in an open\u2010field test. Immunohistochemical examination at 14\u2009weeks after AAV\u2010NL2 injection revealed the expression of exogenous <jats:italic>NL2<\/jats:italic> in broad areas of the brain, including the hippocampus and, in these areas, <jats:italic>NL2<\/jats:italic> co\u2010localized with postsynaptic inhibitory molecule gephyrin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Global brain delivery of NL2 by systemic administration of AAV vector may provide a non\u2010invasive therapeutic approach for generalized epilepsy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3402","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T08:31:12Z","timestamp":1639384272000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Global brain delivery of neuroligin 2 gene ameliorates seizures in a mouse model of epilepsy"],"prefix":"10.1002","volume":"24","author":[{"given":"Keiji","family":"Oguro","sequence":"first","affiliation":[{"name":"Department of Neurosurgery International University of Health and Welfare, Shioya Hospital  Tochigi Japan"},{"name":"Department of Neurosurgery Jichi Medical University  Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuniko","family":"Shimazaki","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Jichi Medical University  Tochigi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Yokota","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Jichi Medical University  Tochigi Japan"},{"name":"Department of Neurosurgery Koga Red Cross Hospital  Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Onuki","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Jichi Medical 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