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Adeno-Associated Virus Vector-Mediated Expression of Neuroligin 2 in the Mouse Hippocampus Attenuates the Progression of Pentylenetetrazol-Induced Seizures.

Created on 08 Oct 2026

Authors

Tomohiro Tokutake, Akane Hara, Ayano Murayama, Yuto Mitsuda, Jun Yokose, Yusuke Yano, Yuki Shigetsura, Mika Ito, Naomi Takino, Shinichi Kumagai, Kuniko Shimazaki, Shin-Ichi Muramatsu, Atsumi Nitta

Published in

The journal of gene medicine. Volume 28. Issue 10. Pages e70116.

Abstract

Gene therapy can target specific brain regions and may be an effective therapeutic tool for drug-resistant epilepsy. Neuroligin 2 (NL2) is a postsynaptic cell-adhesion protein involved in the formation of inhibitory synapses. Since epileptic seizures are attributed to excessive brain neuronal activity, we hypothesized that NL2-mediated inhibitory signaling suppresses seizures. Male C57BL/6J mice were bilaterally injected into the hippocampus (HPC) with an adeno-associated virus (AAV) vector expressing NL2 under the control of synapsin I promoter (AAV-NL2). Mice treated with AAV-NL2 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-Fos protein levels were significantly suppressed with AAV-NL2 injection. NL2 expression induced by intra-HPC AAV-NL2 injection attenuates the progression of PTZ-induced seizures and may represent a potential target for seizure control.

PMID:
42844949
Bibliographic data and abstract were imported from PubMed on 08 Oct 2026.

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