title: Rosiglitazone prevents the memory deficits induced by amyloid-beta oligomers via inhibition of inflammatory responses.
abstract: Rosiglitazone has been known to attenuate neurodegeneration in Alzheimer's disease (AD), but the underlying mechanisms remain unclear. In this study, Morris water maze test, ELISA and electrophysiological methods were used to examine the role and underling mechanisms of rosiglitazone on Aβ42 oligomer-induced memory impairments. We found that rosiglitazone attenuated Aβ42 oligomer-induced memory impairments in rats in a dose-dependent manner. The levels of inflammatory cytokines interleukin-1 beta (IL-1β) and interferon gamma (IFNγ) were significantly increased 7 days after injection of Aβ42 oligomers into the rat hippocampus. Inhibition of microglia activation prevented Aβ42 oligomer-induced increases in IL-1β and IFNγ levels. Rosiglitazone completely prevented the increase in the levels of IL-1β and IFNγ induced by Aβ42 oligomers. Treatment of hippocampal slices with the inflammatory cytokine IL-1β or IFNγ significantly inhibited the production of long-term potentiation (LTP) in the dentate gyrus. Rosiglitazone prevented the inhibitory effects of inflammatory cytokines on LTP. Thus, inhibition of inflammatory responses may be part of the mechanisms of action of rosiglitazone on preventing memory deficits induced by Aβ42 oligmers.
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Xu
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Guan
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wei
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China.
authors.forename: Bangxu
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: An
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China.
authors.forename: Junfang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Chang
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China. Electronic address: mody@ucla.edu.
authors.forename: Istvan
authors.initials: I
authors.lastname: Mody
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China. Electronic address: wangqinwen@nbu.edu.cn.
authors.forename: Qinwen
authors.initials: Q
authors.lastname: Wang
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D003072:Cognition Disorders / Q000517:prevention & control; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D018836:Inflammation Mediators / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000517:prevention & control*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D016229:Amyloid beta-Peptides; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D045162:Thiazolidinediones; C075222:amyloid beta-protein (1-42); D000077154:Rosiglitazone; D007371:Interferon-gamma
keywords: Alzheimer's disease; Amyloid-beta 42 oligomers; Inflammatory cytokines; Long-term potentiation; Rosiglitazone