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
  • View Affiliations

  • 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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October 2012
Volume 30 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Sun J, Xie C, Liu W, Lu D, Qiao W, Huang Q, Huo Z, Shen H and Lin Z: The effects of simvastatin on hippocampal caspase-3 and Bcl-2 expression following kainate-induced seizures in rats. Int J Mol Med 30: 739-746, 2012.
APA
Sun, J., Xie, C., Liu, W., Lu, D., Qiao, W., Huang, Q. ... Lin, Z. (2012). The effects of simvastatin on hippocampal caspase-3 and Bcl-2 expression following kainate-induced seizures in rats. International Journal of Molecular Medicine, 30, 739-746. https://doi.org/10.3892/ijmm.2012.1076
MLA
Sun, J., Xie, C., Liu, W., Lu, D., Qiao, W., Huang, Q., Huo, Z., Shen, H., Lin, Z."The effects of simvastatin on hippocampal caspase-3 and Bcl-2 expression following kainate-induced seizures in rats". International Journal of Molecular Medicine 30.4 (2012): 739-746.
Chicago
Sun, J., Xie, C., Liu, W., Lu, D., Qiao, W., Huang, Q., Huo, Z., Shen, H., Lin, Z."The effects of simvastatin on hippocampal caspase-3 and Bcl-2 expression following kainate-induced seizures in rats". International Journal of Molecular Medicine 30, no. 4 (2012): 739-746. https://doi.org/10.3892/ijmm.2012.1076