Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8840783 | Neuroscience | 2018 | 27 Pages |
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra, leading to motor dysfunction. Growing evidence has demonstrated that endurance exercise (EE) confers neuroprotection against PD. However, the exact molecular mechanisms responsible for exercise-induced protection of dopaminergic neurons in PD remain unclear. Since oxidative stress plays a key role in the degenerative process of PD. We investigated whether EE-induced neuroprotection is associated with enhanced antioxidative capacity and autophagy, using a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. C57BL/6 male mice were randomly assigned to four groups: control (CON, nâ¯=â¯12), exercise (EXE, nâ¯=â¯12), MPTP (MPTP, nâ¯=â¯12) and MPTPâ¯+â¯exercise (MPTPâ¯+â¯EXE, nâ¯=â¯12). Our data demonstrated that while MPTP treatment impaired motor function, EE restored MPTP-induced motor deficits. Our biochemical data showed that EE-induced neuroprotection occurs in combination with multiple synergic neuroprotective pathways: (1) increased neurogenesis shown by an increase in BrdU-positive neurons; (2) diminished loss of dopaminergic neurons evidenced by upregulated tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels; (3) increased antioxidant capacity (e.g., CuZnSOD, CATALASE, GPX1/2, HO-1, DJ1 and PRXIII); and (4) enhanced autophagy (LC3 II, p62, BECLIN1, BNIP3, LAMP2, CATHEPSIN L and TFEB). Our study suggests that EE-induced multiple synergic protective pathways including enhanced neurogenesis, antioxidative capacity, and concordant autophagy promotion contribute to restoration of impaired dopaminergic neuronal function caused by PD. Thus, PD patients should be encouraged to actively participate in regular EE as a potent nonpharmacological therapeutic strategy against PD.
Keywords
DATPeroxiredoxin IIInuclear factor erythroid 2SVZMnSODMPTPCuZnSODHO-1GPXNrf21-methyl-4-phenyl-1,2,3,6-tetrahydropyridine5-bromo-2′-deoxyuridineROSSNpcAntioxidantAutophagyDopamine transporterBrdUParkinson’s diseaseParkinson's diseaseOxidative stresssubstantia nigra pars compactatyrosine hydroxylasemanganese superoxide dismutasecopper zinc superoxide dismutasedentate gyrussubventricular zoneNeurogenesisEndurance exerciseglutathione peroxidaseReactive oxygen species
Related Topics
Life Sciences
Neuroscience
Neuroscience (General)
Authors
Yongchul Jang, Insu Kwon, Wankeun Song, Ludmila M. Cosio-Lima, Youngil Lee,