Nrf2-ARE signals mediated the anti-oxidative action of electroacupuncture in an MPTP mouse model of Parkinson's disease

Abstract

Oxidative stress and neuroinflammation are early events associated with dopaminergic neuronal degeneration in Parkinson's disease (PD). Previous studies indicated that electroacupuncture (EA) stimulation is effective in protecting dopaminergic neurons from degeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In this study, we further characterized the effect of EA on MPTP-induced oxidative responses in the mouse dopamine system. We found that subacute administration of MPTP enhanced lipid and protein oxidation and reduced expression of endogenous antioxidant enzymes (such as superoxide dismutase and catalase) in the striatum. MPTP also reduced expression of an antioxidant transcription factor, nuclear factor-E2-related factor-2 (Nrf2), and Nrf2-regulated antioxidant enzymes (nicotinamide adenine dinucleotide phosphate quinone oxidoreductase-1 and heme oxygenase-1) in the striatum and/or midbrain. Using human placental alkaline phosphatase (hPAP) as a reporter of Nrf2-regulated gene expression in hPAP transgenic mice, we found that MPTP suppressed hPAP expression in the striatum and midbrain. Application of EA at an effective frequency (100 Hz) was sufficient to reverse these changes induced by MPTP. In addition, EA reduced microglia activation and astrogliosis in the striatum and midbrain, increased tyrosine hydroxylase levels in the striatum, and improved vertical movement in MPTP mice. These results provide further evidence supporting that EA produces a series of anti-oxidative effects that effectively counteract with the oxidative stress in the nigrostriatal dopamine system induced by MPTP in a mouse model of PD.

Keywords::

• Parkinson's disease
• electroacupuncture
• anti-oxidative stress
• anti-inflammation
• Nrf2-ARE pathway

Acknowledgments

The study was supported by the National Basic Research Program of China (2011CB504100), the National Natural Science Foundation of China (81072858, 81473770, and 81030062), Beijing Natural Science Foundation (7152021), the Importation and Development of High-Caliber Talents Project of Beijing Municipal Institutions (CIT&TCD201304185), the Project of Construction of Innovative Teams and Teacher Career Development for Universities and Colleges under the Beijing Municipality (IDHT20140514), and the Seed Grant of International Alliance of Translational Neuroscience (PXM2014_ 014226_000015), the program of Key Laboratory for Neurodegenerative Diseases(2013SJBX04). We express our sincere thanks to Dr. John Q. Wang (University of Missouri-Kansas City) for his critical readings of the manuscript.

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.