Atorvastatin Attenuates Cognitive Deficits and Neuroinflammation Induced by Aβ1–42 Involving Modulation of TLR4/TRAF6/NF-κB Pathway

Autor: Hongshan Chu, Shan Wang, Liuyu Zhai, Weina Zheng, Xiaowei Zhang, Guohua Zhang, Xiaona Sheng
Rok vydání: 2018
Předmět:
Zdroj: Journal of Molecular Neuroscience. 64:363-373
ISSN: 1559-1166
0895-8696
DOI: 10.1007/s12031-018-1032-3
Popis: Inflammatory damage aggravates the progression of Alzheimer’s disease (AD) and the mechanism of inflammatory damage may provide a new therapeutic window for the treatment of AD. Toll-like receptor 4 (TLR4)-mediated signaling can regulate the inflammatory process. However, changes in TLR4 signaling pathway induced by beta-amyloid (Aβ) have not been well characterized in brain, especially in the hippocampus. In the present study, we explored the changes of TLR4 signaling pathway induced by Aβ in the hippocampus and the role of atorvastatin in modulating this signal pathway and neurotoxicity induced by Aβ. Experimental AD rats were induced by intrahippocampal injection of Aβ1–42, and the rats were treated with atorvastatin by oral gavage from 3 weeks before to 6 days after injections of Aβ1–42. To determine the spatial learning and memory ability of rats in the AD models, Morris water maze (MWM) was performed. The expression of the glial fibrillary acidic protein (GFAP), ionized calcium binding adapter molecule-1 (Iba-1), TLR4, tumor necrosis factor receptor-associated factor 6 (TRAF6), and nuclear transcription factor (NF)-κB (NF-κB) protein in the hippocampus was detected by immunohistochemistry and Western blot. Compared to the control group, increased expression of TLR4, TRAF6, and NF-κB was observed in the hippocampus at 7 days post-injection of Aβ (P
Databáze: OpenAIRE
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