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Research Paper|Volume 13, Issue 1|pp 831—845

Atorvastatin improves motor function, anxiety and depression by NOX2-mediated autophagy and oxidative stress in MPTP-lesioned mice

Junqiang Yan1,2, Jiarui Huang2, Anran Liu2, Jiannan Wu1, Hua Fan3, Mengmeng Shen1, Xiaoyi Lai1, Hongxia Ma2, Wenjie Sun2, Jianxue Yang4, Yunqi Xu5
  • 1Neuromolecular Biology Laboratory, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, P.R. China
  • 2Department of Neurology, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, P.R. China
  • 3Department of Pharmacy, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, P.R. China
  • 4School of Nursing of Henan University of Science and Technology, Luoyang 471003, P.R. China
  • 5Department of Neurology, Nanfang Hospital of Southern Medical University, Guangzhou 510515, P.R. China
Received: March 28, 2020Accepted: October 20, 2020Published: December 3, 2020
https://doi.org/10.18632/aging.202189

Copyright: © 2020 Yan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Parkinson’s disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons. It is characterized by static tremors, stiffness, slow movements, and gait disturbances, but it is also accompanied by anxiety and depression. Our previous study showed that atorvastatin could reduce the risk of PD, but the mechanism is still unclear. In this paper, Our findings showed that atorvastatin increased muscle capacity and the coordination of movement and improved anxiety and depression. Atorvastatin could decrease the expression of α-synuclein Ser129 and NADPH oxidase 2 (NOX2), increase the protein expression of LC3II/I, and promote autophagy flow. To further confirm that atorvastatin protection was achieved by inhibiting NOX2, we injected at midbrain with NOX2 shRNA (M) lentivirus and found that silent NOX2 produced the same effect as atorvastatin. Further research found that atorvastatin could reduce MPTP-induced oxidative stress damage, while inhibiting NOX2 decreased the antioxidative stress effect of atorvastatin. Our results suggest that atorvastatin can improve muscle capacity, anxiety and depression by inhibiting NOX2, which may be related to NOX2-mediated oxidative stress and autophagy. Atorvastatin may be identified as a drug that can effectively improve behavioral disorders. NOX2 may be a potential gene target for new drug development in PD.