Protective effects of peroxisome proliferator-activated receptors γ coactivator-1α against neuronal cell death in the hippocampal CA1 subfield after transient global ischemia

Shang Der Chen, Tsu Kung Lin, Ding I. Yang, Su Ying Lee, Fu Zen Shaw, Chia Wei Liou, Yao Chung Chuang

研究成果: Article同行評審

57 引文 斯高帕斯(Scopus)

摘要

Peroxisome proliferator-activated receptors γ coactivator-1α (PGC-1α) may regulate the mitochondrial antioxidant defense system under many neuropathological settings. However, the exact role of PGC-1α in ischemic brain damage is still under debate. Based on an experimental model of transient global ischemia (TGI), this study evaluated the hypothesis that the activation of PGC-1α signaling pathway protects hippocampal CA1 neurons against delayed neuronal death after TGI. In Sprague-Dawley rats, significantly increased content of oxidized proteins in the hippocampal CA1 tissue was observed as early as 30 min after TGI, followed by augmentation of PGC-1α expression at 1 hr. Expression of uncoupling protein 2 (UCP2) and superoxide dismutases 2 (SOD2) in the hippocampal CA1 neurons was upregulated 4-48 hr after TGI. In addition, knock-down of PGC-1α expression by pretreatment with a specific antisense oligodeoxynucleotide in the hippocampal CA1 subfield downregulated the expression of UCP2 and SOD2 with resultant exacerbation of oxidative stress and augmentation of delayed neuronal cell death in the hippocampus after TGI. Overall, our results indicate that PGC-1α is induced by cerebral ischemia leading to upregulation of UCP2 and SOD2, thereby providing a neuroprotective effect against ischemic brain injury in the hippocampus by ameliorating oxidative stress.

原文English
頁(從 - 到)605-613
頁數9
期刊Journal of Neuroscience Research
88
發行號3
DOIs
出版狀態Published - 2010 二月 15

All Science Journal Classification (ASJC) codes

  • 細胞與分子神經科學

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