Modulation of Preactivation of PPAR-β on Memory and Learning Dysfunction and Inflammatory Response in the Hippocampus in Rats Exposed to Global Cerebral Ischemia/Reperfusion

The aim of this study is to investigate the neuroprotective effects and relevant mechanism of GW0742, an agonist of PPAR-β, after global cerebral ischemia-reperfusion injury (GCIRI) in rats. The rats showed memory and cognitive impairment and cytomorphological change in the hippocampus neurons follo...

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Main Authors: Ge Kuang, Qin He, Yunmei Zhang, Ruichun Zhuang, Anling Xiang, Qingsong Jiang, Ying Luo, Junqing Yang
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:PPAR Research
Online Access:http://dx.doi.org/10.1155/2012/209794
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author Ge Kuang
Qin He
Yunmei Zhang
Ruichun Zhuang
Anling Xiang
Qingsong Jiang
Ying Luo
Junqing Yang
author_facet Ge Kuang
Qin He
Yunmei Zhang
Ruichun Zhuang
Anling Xiang
Qingsong Jiang
Ying Luo
Junqing Yang
author_sort Ge Kuang
collection DOAJ
description The aim of this study is to investigate the neuroprotective effects and relevant mechanism of GW0742, an agonist of PPAR-β, after global cerebral ischemia-reperfusion injury (GCIRI) in rats. The rats showed memory and cognitive impairment and cytomorphological change in the hippocampus neurons following GCIRI. These effects were significantly improved by pretreatment with GW0742 in the dose-dependent manner. The expressions of IL-1β, IL-6, and TNF-α were increased after GCIRI, while the increases in these proinflammatory cytokines by GCIRI were inhibited by GW0742 pretreatment. Similarly, GW0742 pretreatment also improved the GCIRI-induced decrease in the expression of IL-10, which can act as an inhibitory cytokine to reduce cerebral ischemic injury. For another, NF-κB p65 expression was significantly increased in hippocampal neurons with apparent nuclear translocation after global cerebral IRI, and these phenomena were also largely attenuated by GW0742 pretreatment. Moreover, the mRNA and protein expressions of PPAR-β were significantly decreased in GCIRI + GW0742 groups when compared with those in GCIRI group. Our data suggests that the PPAR-β agonist GW0742 can exert significant neuroprotective effect against GCIRI in rats via PPAR-β activation and its anti-inflammation effect mediated by the inhibition of expression and activation of NF-κB in the hippocampus.
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spelling doaj-art-e724e9d7ca894ae49d7a8e6459e3acfb2025-02-03T05:47:14ZengWileyPPAR Research1687-47571687-47652012-01-01201210.1155/2012/209794209794Modulation of Preactivation of PPAR-β on Memory and Learning Dysfunction and Inflammatory Response in the Hippocampus in Rats Exposed to Global Cerebral Ischemia/ReperfusionGe Kuang0Qin He1Yunmei Zhang2Ruichun Zhuang3Anling Xiang4Qingsong Jiang5Ying Luo6Junqing Yang7Department of Pharmacology, The College of Pharmacy, Chongqing Medical University, Chongqing 400010, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400010, ChinaDepartment of Nursing, Nursing School of Chongqing Medical University, Chongqing 400010, ChinaDepartment of Pharmacology, The College of Pharmacy, Chongqing Medical University, Chongqing 400010, ChinaDepartment of Pharmacology, The College of Pharmacy, Chongqing Medical University, Chongqing 400010, ChinaDepartment of Pharmacology, The College of Pharmacy, Chongqing Medical University, Chongqing 400010, ChinaDepartment of Pharmacology, The College of Pharmacy, Chongqing Medical University, Chongqing 400010, ChinaDepartment of Pharmacology, The College of Pharmacy, Chongqing Medical University, Chongqing 400010, ChinaThe aim of this study is to investigate the neuroprotective effects and relevant mechanism of GW0742, an agonist of PPAR-β, after global cerebral ischemia-reperfusion injury (GCIRI) in rats. The rats showed memory and cognitive impairment and cytomorphological change in the hippocampus neurons following GCIRI. These effects were significantly improved by pretreatment with GW0742 in the dose-dependent manner. The expressions of IL-1β, IL-6, and TNF-α were increased after GCIRI, while the increases in these proinflammatory cytokines by GCIRI were inhibited by GW0742 pretreatment. Similarly, GW0742 pretreatment also improved the GCIRI-induced decrease in the expression of IL-10, which can act as an inhibitory cytokine to reduce cerebral ischemic injury. For another, NF-κB p65 expression was significantly increased in hippocampal neurons with apparent nuclear translocation after global cerebral IRI, and these phenomena were also largely attenuated by GW0742 pretreatment. Moreover, the mRNA and protein expressions of PPAR-β were significantly decreased in GCIRI + GW0742 groups when compared with those in GCIRI group. Our data suggests that the PPAR-β agonist GW0742 can exert significant neuroprotective effect against GCIRI in rats via PPAR-β activation and its anti-inflammation effect mediated by the inhibition of expression and activation of NF-κB in the hippocampus.http://dx.doi.org/10.1155/2012/209794
spellingShingle Ge Kuang
Qin He
Yunmei Zhang
Ruichun Zhuang
Anling Xiang
Qingsong Jiang
Ying Luo
Junqing Yang
Modulation of Preactivation of PPAR-β on Memory and Learning Dysfunction and Inflammatory Response in the Hippocampus in Rats Exposed to Global Cerebral Ischemia/Reperfusion
PPAR Research
title Modulation of Preactivation of PPAR-β on Memory and Learning Dysfunction and Inflammatory Response in the Hippocampus in Rats Exposed to Global Cerebral Ischemia/Reperfusion
title_full Modulation of Preactivation of PPAR-β on Memory and Learning Dysfunction and Inflammatory Response in the Hippocampus in Rats Exposed to Global Cerebral Ischemia/Reperfusion
title_fullStr Modulation of Preactivation of PPAR-β on Memory and Learning Dysfunction and Inflammatory Response in the Hippocampus in Rats Exposed to Global Cerebral Ischemia/Reperfusion
title_full_unstemmed Modulation of Preactivation of PPAR-β on Memory and Learning Dysfunction and Inflammatory Response in the Hippocampus in Rats Exposed to Global Cerebral Ischemia/Reperfusion
title_short Modulation of Preactivation of PPAR-β on Memory and Learning Dysfunction and Inflammatory Response in the Hippocampus in Rats Exposed to Global Cerebral Ischemia/Reperfusion
title_sort modulation of preactivation of ppar β on memory and learning dysfunction and inflammatory response in the hippocampus in rats exposed to global cerebral ischemia reperfusion
url http://dx.doi.org/10.1155/2012/209794
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