Atorvastatin Attenuates Cognitive Deficits and Neuroinflammation Induced by A beta(1-42) Involving Modulation of TLR4/TRAF6/NF-kappa B Pathway

作者：Wang, Shan; Zhang, Xiaowei; Zhai, Liuyu; Sheng, Xiaona^*; Zheng, Weina; Chu, Hongshan; Zhang, Guohua

来源：Journal of Molecular Neuroscience, 2018, 64(3): 363-373.

DOI：10.1007/s12031-018-1032-3

• Atorvastatin
• Alzheimer's disease
• Protection
• TLR4
• TRAF6
• NF-kappa B

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 (A beta) 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 A beta in the hippocampus and the role of atorvastatin in modulating this signal pathway and neurotoxicity induced by A beta. Experimental AD rats were induced by intrahippocampal injection of A beta(1-42), and the rats were treated with atorvastatin by oral gavage from 3 weeks before to 6 days after injections of A beta(1-42). 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)-kappa B (NF-kappa B) protein in the hippocampus was detected by immunohistochemistry and Western blot. Compared to the control group, increased expression of TLR4, TRAF6, and NF-kappa B was observed in the hippocampus at 7 days post-injection of A beta (P < 0.01). Furthermore, atorvastatin treatment significantly ameliorated cognitive deficits of rats, attenuated microglia and astrocyte activation, inhibited apoptosis, and down-regulated the expression of TLR4, TRAF6, and NF-kappa B, both at the mRNA and protein levels (P < 0.01). TLR4 signaling pathway is thus actively involved in A beta-induced neuroinflammation and atorvastatin treatment can exert the therapeutic benefits for AD via the TLR4 signaling pathway.

• 出版日期2018-3
• 单位河北医科大学