Yongchul Jang1, Insu Kwon2, Wankeun Song2, Ludmila M Cosio-Lima2, Scott Taylor3, Youngil Lee4. 1. Molecular and Cellular Exercise Physiology Laboratory, University of West Florida, 11000 University Pkwy, Bldg.72, Pensacola, FL 32514, USA; Exercise Biochemistry Laboratory, Korea National Sport University, 88-15 Oryun-dong, Songpa-gu, Seoul 138-763, Republic of Korea. 2. Molecular and Cellular Exercise Physiology Laboratory, University of West Florida, 11000 University Pkwy, Bldg.72, Pensacola, FL 32514, USA. 3. Department of Biology, University of West Florida, 11000 University Pkwy, Bldg.58, Pensacola, FL 32514, USA. 4. Molecular and Cellular Exercise Physiology Laboratory, University of West Florida, 11000 University Pkwy, Bldg.72, Pensacola, FL 32514, USA. Electronic address: ylee@uwf.edu.
Abstract
AIM: Endurance exercise (EE) has been reported to confer neuroprotection against Parkinson's disease (PD); however, underlying molecular mechanisms of the protection remain still unclear. Since mitochondrial impairment is commonly observed in the brain of PD patients and animals, this study investigated whether EE-induced neuroprotection is associated with mitochondrial phenotypes, using a mouse model of PD induced by intraperitoneal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MAIN METHODS: SH-SY5Y cells were cultured with a neurotoxin MPP+ known to cause PD-like symptoms to examine if modifications of mitochondrial morphology are linked to etiology of PD. For in vivo experiments, C57BL/6 male mice were randomly assigned to four groups: control (CON, n = 12), endurance exercise (EXE, n = 12), MPTP (MPTP, n = 12) and MPTP plus endurance exercise (MPTP + EXE, n = 12). Mice assigned to endurance exercise performed treadmill running at 12 m/min for 60 min/day, 5 days/week for 6 weeks. KEY FINDINGS: SH-SY5Y cells exposed to a neurotoxin MPP+ exhibited mitochondrial fragmentation and diminished mitochondrial proteins, and cell death. Similarly, animals administered with MPTP displayed comparable impairments in the substantia nigra pars compacta (SNpc). In contrast, EE intervention restored motor function to control levels and reduced apoptosis. These propitious effects of EE were associated with mitochondrial phenotypic changes such as upregulated anti-apoptotic proteins (e.g., MCL-1 and BLC-2), reduced a pro-apoptotic protein (e.g., AIF), and improved mitochondrial biogenesis and fusion. SIGNIFICANCE: Our finding that EE-induced mitochondrial phenotypic changes that resist mitochondrial impairment and cell death against PD introduce potential insight into mitochondria as a new therapeutic target for PD.
AIM: Endurance exercise (EE) has been reported to confer neuroprotection against Parkinson's disease (PD); however, underlying molecular mechanisms of the protection remain still unclear. Since mitochondrial impairment is commonly observed in the brain of PDpatients and animals, this study investigated whether EE-induced neuroprotection is associated with mitochondrial phenotypes, using a mouse model of PD induced by intraperitoneal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MAIN METHODS:SH-SY5Y cells were cultured with a neurotoxin MPP+ known to cause PD-like symptoms to examine if modifications of mitochondrial morphology are linked to etiology of PD. For in vivo experiments, C57BL/6 male mice were randomly assigned to four groups: control (CON, n = 12), endurance exercise (EXE, n = 12), MPTP (MPTP, n = 12) and MPTP plus endurance exercise (MPTP + EXE, n = 12). Mice assigned to endurance exercise performed treadmill running at 12 m/min for 60 min/day, 5 days/week for 6 weeks. KEY FINDINGS:SH-SY5Y cells exposed to a neurotoxin MPP+ exhibited mitochondrial fragmentation and diminished mitochondrial proteins, and cell death. Similarly, animals administered with MPTP displayed comparable impairments in the substantia nigra pars compacta (SNpc). In contrast, EE intervention restored motor function to control levels and reduced apoptosis. These propitious effects of EE were associated with mitochondrial phenotypic changes such as upregulated anti-apoptotic proteins (e.g., MCL-1 and BLC-2), reduced a pro-apoptotic protein (e.g., AIF), and improved mitochondrial biogenesis and fusion. SIGNIFICANCE: Our finding that EE-induced mitochondrial phenotypic changes that resist mitochondrial impairment and cell death against PD introduce potential insight into mitochondria as a new therapeutic target for PD.