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

50 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

Fingerprint

Peroxisome Proliferator-Activated Receptors
Cell Death
Ischemia
Hippocampus
Oxidative Stress
Neurons
Oligodeoxyribonucleotides
Neuroprotective Agents
Brain Ischemia
Brain Injuries
Sprague Dawley Rats
Theoretical Models
Up-Regulation
Down-Regulation
Antioxidants
Brain
Uncoupling Protein 2
superoxide dismutase 2
Proteins

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

@article{d5d528c9c9d945bfa44d92b136f502e3,
title = "Protective effects of peroxisome proliferator-activated receptors γ coactivator-1α against neuronal cell death in the hippocampal CA1 subfield after transient global ischemia",
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.",
author = "Chen, {Shang Der} and Lin, {Tsu Kung} and Yang, {Ding I.} and Lee, {Su Ying} and Fu-Zen Shaw and Liou, {Chia Wei} and Chuang, {Yao Chung}",
year = "2010",
month = "2",
day = "15",
doi = "10.1002/jnr.22225",
language = "English",
volume = "88",
pages = "605--613",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "3",

}

Protective effects of peroxisome proliferator-activated receptors γ coactivator-1α against neuronal cell death in the hippocampal CA1 subfield after transient global ischemia. / Chen, Shang Der; Lin, Tsu Kung; Yang, Ding I.; Lee, Su Ying; Shaw, Fu-Zen; Liou, Chia Wei; Chuang, Yao Chung.

In: Journal of Neuroscience Research, Vol. 88, No. 3, 15.02.2010, p. 605-613.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Protective effects of peroxisome proliferator-activated receptors γ coactivator-1α against neuronal cell death in the hippocampal CA1 subfield after transient global ischemia

AU - Chen, Shang Der

AU - Lin, Tsu Kung

AU - Yang, Ding I.

AU - Lee, Su Ying

AU - Shaw, Fu-Zen

AU - Liou, Chia Wei

AU - Chuang, Yao Chung

PY - 2010/2/15

Y1 - 2010/2/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=73949136761&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73949136761&partnerID=8YFLogxK

U2 - 10.1002/jnr.22225

DO - 10.1002/jnr.22225

M3 - Article

VL - 88

SP - 605

EP - 613

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 3

ER -