The effects of simvastatin on hippocampal caspase-3 and Bcl-2 expression following kainate-induced seizures in rats

Sun,Jiahang; Xie,Chuncheng; Liu,Wei; Lu,Dunyue; Qiao,Weidong; Huang,Qi; Huo,Zhihui; Shen,Hong; Lin,Zhiguo

doi:10.3892/ijmm.2012.1076

The effects of simvastatin on hippocampal caspase-3 and Bcl-2 expression following kainate-induced seizures in rats

Authors:
- Jiahang Sun
- Chuncheng Xie
- Wei Liu
- Dunyue Lu
- Weidong Qiao
- Qi Huang
- Zhihui Huo
- Hong Shen
- Zhiguo Lin
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Affiliations: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, P.R. China, Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China, Department of Psychiatry, State University of New York, Downstate Medical Center, Brooklyn, NY, USA, Department of Anatomy, Harbin Medical University, Harbin, P.R. China
Published online on: July 25, 2012 https://doi.org/10.3892/ijmm.2012.1076
Pages: 739-746

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Abstract

Status epilepticus (SE) causes neuronal loss and apoptosis by inducing several apoptosis-regulatory genes. Two such genes, cysteinyl aspartate-specific protease-3 (caspase-3), an apoptosis activator, and B-cell leukemia-2 (Bcl-2), an apoptosis suppressor, are tightly regulated for their expression and activation. Statins, inhibitors of HMG-CoA reductase, have been recently recognized as neuroprotective drugs. However, their underlying mechanisms are still unclear. In this study, we examined the neuroprotective effects of simvastatin in a rat model of SE induced by kainic acid (KA). Feeding of simvastatin for 3 days after kainate injection rescued SE-induced neuronal apoptosis, as determined by histological examination of brain sections at the level of the dorsal hippocampus. Semi-quantitative RT-PCR showed that SE treatment markedly increased caspase-3 mRNA expression and reduced Bcl-2 mRNA expression in the hippocampus. Similarly, western blot analysis and immunohistochemical analysis of the rat hippocampus demonstrated that under SE treatment, caspase-3 protein levels significantly increased and peaked at 72 h, whereas Bcl-2 protein levels decreased from 6-24 h following SE. Interestingly, simvastatin could reverse the aforementioned SE-induced changes, suggesting that the neuroprotective effects of simvastatin against neuronal apoptosis may be achieved by inhibiting caspase-3 expression and increasing Bcl-2 expression.

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