title: 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.
authors.affiliation: a Departments of Neurobiology and Physiology , Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Beijing Key Laboratory for Parkinson's Disease, Capital Medical University; Beijing Institute for Brain Disorders , Beijing , 100069 , China.
authors.forename: E
authors.initials: E
authors.lastname: Lv
authors.affiliation: a Departments of Neurobiology and Physiology , Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Beijing Key Laboratory for Parkinson's Disease, Capital Medical University; Beijing Institute for Brain Disorders , Beijing , 100069 , China.
authors.forename: J
authors.initials: J
authors.lastname: Deng
authors.affiliation: a Departments of Neurobiology and Physiology , Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Beijing Key Laboratory for Parkinson's Disease, Capital Medical University; Beijing Institute for Brain Disorders , Beijing , 100069 , China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.affiliation: a Departments of Neurobiology and Physiology , Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Beijing Key Laboratory for Parkinson's Disease, Capital Medical University; Beijing Institute for Brain Disorders , Beijing , 100069 , China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: a Departments of Neurobiology and Physiology , Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Beijing Key Laboratory for Parkinson's Disease, Capital Medical University; Beijing Institute for Brain Disorders , Beijing , 100069 , China.
authors.forename: X
authors.initials: X
authors.lastname: Gong
authors.affiliation: a Departments of Neurobiology and Physiology , Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Beijing Key Laboratory for Parkinson's Disease, Capital Medical University; Beijing Institute for Brain Disorders , Beijing , 100069 , China.
authors.forename: J
authors.initials: J
authors.lastname: Jia
authors.affiliation: a Departments of Neurobiology and Physiology , Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Beijing Key Laboratory for Parkinson's Disease, Capital Medical University; Beijing Institute for Brain Disorders , Beijing , 100069 , China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000276:immunology*; D000818:Animals; D004195:Disease Models, Animal; D015671:Electroacupuncture / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051267:NF-E2-Related Factor 2; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
keywords: Nrf2-ARE pathway; Parkinson's disease; anti-inflammation; anti-oxidative stress; electroacupuncture