Ectopic expression of Miro 1 ameliorates seizures and inhibits hippocampal neurodegeneration in a mouse model of pilocarpine epilepsy.

Abstract

Epilepsy is a common disease of the central nervous system. This study aimed to investigate the role of mitochondrial Rho (Miro) 1 in epilepsy, using a mouse model of pilocarpine-induced status epilepticus (SE). Intraperitoneal injection of pilocarpine induced epileptic seizures in mice and significantly decreased Miro 1 expression in the hippocampus. Moreover, pilocarpine treatment increased the serum levels of heat shock protein 70 (HSP70) and S100 calcium binding protein B (S100B) and led to hippocampal neuronal injury and apoptosis. The intrinsic apoptotic pathway was activated in the hippocampal neurons following pilocarpine-induced SE, as evidenced by increased levels of cleaved caspase-3 and Bax, downregulation of Bcl-2, and the release of cytochrome c from mitochondria to cytoplasm. By contrast, forced expression of Miro 1 by lateral ventricular administration of adenovirus mitigated pilocarpine-induced epileptic seizures, reduced the elevation of HSP70 and S100B, and inhibited hippocampal neuronal apoptosis by suppressing the intrinsic apoptotic pathway. In summary, our data demonstrates that ectopic expression of Miro 1 alleviated pilocarpine-induced SE and protected hippocampal neurons by inhibiting the intrinsic apoptotic pathway. These findings provide new insights into epileptic disorders and suggest a potential neuroprotective value of Miro 1 in the treatment of epilepsy.