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

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)605-613
Number of pages9
JournalJournal of Neuroscience Research
Volume88
Issue number3
DOIs
Publication statusPublished - 2010 Feb 15

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Protective effects of peroxisome proliferator-activated receptors γ coactivator-1α against neuronal cell death in the hippocampal CA1 subfield after transient global ischemia'. Together they form a unique fingerprint.

  • Cite this