Stability of nNOS in generalized epilepsy

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The major aim of this study was to elucidate relationship between NOS-dependent NO and generalized epilepsy. Pentylenetetrazole (PTZ) was used to induce kindling in mouse as animal model of generalized epilepsy. The daily administration of PTZ is associated with increases in the amount and activities of nNOS and NO production. To confirm the relationship between nNOS and NO, mice lacking nNOS gene (nNOS-/-mice) were used to observe the development of PTZ kindling. nNOS-/-mice exhibited more severe seizures following injection with PTZ (40 mg/kg) and during the development of PTZ (30 mg/kg) kindling. Thus, the behavioral evidence indicated that nNOS might be related to PTZ-induced seizures in mice, but not to the development of PTZ-induced kindling.To confirm the increase in sensitivity of PTZ in nNOS-/-mice, wild type (nNOS+/+) mice were treated with nNOS inhibitor, TRIM (1-(2-trifluoromethylphenyl)imidazole) and measured sizure scores. The nNOS+/+ mouse treated with TRIM were dose-dependently enhanced PTZ-induced tonic-clonic convulsions. The enhancement of tonic-clonic convulsions by TRIM was coincident with the increase in sensitivity of PTZ in nNOS-/-mice. Therefore, these results suggest that the normal activation of glutamatergic neurons could be regulated by basal activity of NO. On the other hand, the overactivation of glutamatergic neurons by PTZ might be accelerated by NO which was synthesized by the activation of nNOS through NMDAR.