Journal of Molecular Neuroscience

, Volume 64, Issue 3, pp 363–373 | Cite as

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

  • Shan Wang
  • Xiaowei Zhang
  • Liuyu Zhai
  • Xiaona Sheng
  • Weina Zheng
  • Hongshan Chu
  • Guohua Zhang
Article
  • 187 Downloads

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.

Keywords

Atorvastatin Alzheimer’s disease Protection TLR4 TRAF6 NF-κB 

Notes

Acknowledgements

We gratefully acknowledge the technical support and helpful discussions of our colleagues and collaborators.

Author Contributions

S.W. and X.W.Z. prepared the manuscript and were participated in the data analysis; L.Y.Z. was involved in the data analysis; X.N.S. and W.N.Z. collected data; H.S.C. and G.H.Z. designed this study and guided the data analysis. All authors have read and approved the final manuscript.

Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 1.Department of NeurologyThe Second Hospital of Hebei Medical UniversityShijiazhuangChina
  2. 2.Department of NeurosurgeryThe Second Hospital of Hebei Medical UniversityShijiazhuangChina

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