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Atorvastatin Attenuates Cognitive Deficits and Neuroinflammation Induced by Aβ1-42 Involving Modulation of TLR4/TRAF6/NF-κB Pathway.
J Mol Neurosci. 2018 Mar; 64(3):363-373.JM

Abstract

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 < 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-κB, both at the mRNA and protein levels (P < 0.01). TLR4 signaling pathway is thus actively involved in Aβ-induced neuroinflammation and atorvastatin treatment can exert the therapeutic benefits for AD via the TLR4 signaling pathway.

Authors+Show Affiliations

Department of Neurology, The Second Hospital of Hebei Medical University, No. 215 Hepingxi Road, Shijiazhuang, Hebei, 050000, China.Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, China.Department of Neurology, The Second Hospital of Hebei Medical University, No. 215 Hepingxi Road, Shijiazhuang, Hebei, 050000, China.Department of Neurology, The Second Hospital of Hebei Medical University, No. 215 Hepingxi Road, Shijiazhuang, Hebei, 050000, China. xnsheng848@126.com.Department of Neurology, The Second Hospital of Hebei Medical University, No. 215 Hepingxi Road, Shijiazhuang, Hebei, 050000, China.Department of Neurology, The Second Hospital of Hebei Medical University, No. 215 Hepingxi Road, Shijiazhuang, Hebei, 050000, China.Department of Neurology, The Second Hospital of Hebei Medical University, No. 215 Hepingxi Road, Shijiazhuang, Hebei, 050000, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29417448

Citation

Wang, Shan, et al. "Atorvastatin Attenuates Cognitive Deficits and Neuroinflammation Induced By Aβ1-42 Involving Modulation of TLR4/TRAF6/NF-κB Pathway." Journal of Molecular Neuroscience : MN, vol. 64, no. 3, 2018, pp. 363-373.
Wang S, Zhang X, Zhai L, et al. Atorvastatin Attenuates Cognitive Deficits and Neuroinflammation Induced by Aβ1-42 Involving Modulation of TLR4/TRAF6/NF-κB Pathway. J Mol Neurosci. 2018;64(3):363-373.
Wang, S., Zhang, X., Zhai, L., Sheng, X., Zheng, W., Chu, H., & Zhang, G. (2018). Atorvastatin Attenuates Cognitive Deficits and Neuroinflammation Induced by Aβ1-42 Involving Modulation of TLR4/TRAF6/NF-κB Pathway. Journal of Molecular Neuroscience : MN, 64(3), 363-373. https://doi.org/10.1007/s12031-018-1032-3
Wang S, et al. Atorvastatin Attenuates Cognitive Deficits and Neuroinflammation Induced By Aβ1-42 Involving Modulation of TLR4/TRAF6/NF-κB Pathway. J Mol Neurosci. 2018;64(3):363-373. PubMed PMID: 29417448.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Atorvastatin Attenuates Cognitive Deficits and Neuroinflammation Induced by Aβ1-42 Involving Modulation of TLR4/TRAF6/NF-κB Pathway. AU - Wang,Shan, AU - Zhang,Xiaowei, AU - Zhai,Liuyu, AU - Sheng,Xiaona, AU - Zheng,Weina, AU - Chu,Hongshan, AU - Zhang,Guohua, Y1 - 2018/02/07/ PY - 2017/09/06/received PY - 2018/01/17/accepted PY - 2018/2/9/pubmed PY - 2018/9/6/medline PY - 2018/2/9/entrez KW - Alzheimer’s disease KW - Atorvastatin KW - NF-κB KW - Protection KW - TLR4 KW - TRAF6 SP - 363 EP - 373 JF - Journal of molecular neuroscience : MN JO - J. Mol. Neurosci. VL - 64 IS - 3 N2 - 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 < 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-κB, both at the mRNA and protein levels (P < 0.01). TLR4 signaling pathway is thus actively involved in Aβ-induced neuroinflammation and atorvastatin treatment can exert the therapeutic benefits for AD via the TLR4 signaling pathway. SN - 1559-1166 UR - https://www.unboundmedicine.com/medline/citation/29417448/Atorvastatin_Attenuates_Cognitive_Deficits_and_Neuroinflammation_Induced_by_Aβ1_42_Involving_Modulation_of_TLR4/TRAF6/NF_κB_Pathway_ L2 - https://dx.doi.org/10.1007/s12031-018-1032-3 DB - PRIME DP - Unbound Medicine ER -