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

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.