Abstracts

Rationale: Status epilepticus (SE) is a common neuronal disorder defined by persistent seizures and accompanied by oxidative brain damage. Chronic epilepsy can develop over time with interspersed latent periods. In its acute phase, excessive oxidative stress in epilepsy can cause neuronal cell death, a key factor in the progression of epileptogenesis. Sirtuin3 (Sirt3), an NAD⁺-dependent histone deacetylase, regulates manganese superoxide dismutase (MnSOD), a major antioxidant enzyme that contributes to aging and neurodegeneration. Here, we investigated the effect of Sirt3 deficiency on neuronal damage and epileptogenesis after pilocarpine-induced SE.

Methods: Pilocarpine was administered to Sirt3 knock-out (KO) and wild-type (WT) C57BL/6 mice. Seizure onset, spontaneous recurrent seizures, and mortality were evaluated. Two months after pilocarpine-induced SE, hippocampal damage and alterations in astrocytes and MnSOD activity were evaluated during the latent period.

Results: Sirt3 KO mice exhibited an increased mortality rate, but there was no difference between KO and WT mice in seizure onset time after pilocarpine administration. KO mice showed a higher number of spontaneous recurrent seizures and exacerbated hippocampal neuronal loss during the chronic epileptic period. In addition, KO mice exhibited severe gliosis and decreased MnSOD activity.

Conclusions: Sirt3 deficiency may alters the development and severity of spontaneous recurrent seizures during epileptogenesis.

Funding: Please list any funding that was received in support of this abstract.: This study was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (NRF-2015R1D1A1A01059901 and NRF-2018R1D1A1B07046708).