NDLI: PPARδ agonist GW0742 ameliorates Aβ$_{1–42}$-induced hippocampal neurotoxicity in mice

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PPARδ agonist GW0742 ameliorates Aβ$_{1–42}$-induced hippocampal neurotoxicity in mice

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PPARδ agonist GW0742 ameliorates Aβ$_{1–42}$-induced hippocampal neurotoxicity in mice

Content Provider	Springer Nature Link
Author	An, Yun Qi Zhang, Chun Teng Du, Yong Zhang, Ming Tang, Su Su Hu, Mei Long, Yan Sun, Hong Bing Hong, Hao
Copyright Year	2016
Abstract	Amyloid-β deposition is thought to be associated with memory deficits, neuroinflammation, apoptotic responses, and progressive neuronal death manifested in Alzheimer’s disease. Peroxisome proliferator-activated receptor δ (PPARδ) is a transcription factor with potent anti-inflammatory effect. In the current study, the effect of GW0742, a selective PPARδ agonist, on Aβ$_{1–42}$-induced neurotoxicity was investigated in the hippocampus of mice. Intra-hippocampal infusion of aggregated Aβ$_{1–42}$ oligomer (410pmol/mouse) remarkably damaged learning and memory in the Morris water maze (MWM) and Y-maze tests, accompanied by decreased expression of PPARδ in the hippocampus as confirmed by Western blot. Intra-hippocampal infusion of GW0742 (1.06 mM/mouse) significantly improved Aβ$_{1–42}$-induced memory deficits in mice, reversed Aβ$_{1–42}$-induced hippocampal PPARδ down-regulation and repressed Aβ$_{1–42}$-triggered neuroinflammatory and apoptotic responses, indicated by decreased nuclear NF-κB p65, TNF-α, IL-1β as well as a decrease in cleaved caspase-3 and increased ratio of Bcl-2/Bax in the hippocampus. These results suggest that PPARδ activation ameliorates Aβ$_{1–42}$-induced hippocampal neurotoxicity, and it might play a crucial role in Alzheimer’s disease.
Starting Page	663
Ending Page	671
Page Count	9
File Format	PDF
ISSN	08857490
Journal	Metabolic Brain Disease
Volume Number	31
Issue Number	3
e-ISSN	15737365
Language	English
Publisher	Springer US
Publisher Date	2016-02-11
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Peroxisome proliferator-activated receptor δ Amyloid-β$_{1–42}$ Neurotoxicity Memory Neurosciences Neurology Metabolic Diseases Biochemistry Oncology
Content Type	Text
Resource Type	Article
Subject	Biochemistry Neurology (clinical) Cellular and Molecular Neuroscience

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PPARδ agonist GW0742 ameliorates Aβ$_{1–42}$-induced hippocampal neurotoxicity in mice

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