Aderbal Silva Aguiar1,2,3, Marcelo Duzzioni4, Aline Pertile Remor5, Fabrine Sales Massafera Tristão6, Filipe C Matheus4, Rita Raisman-Vozari6, Alexandra Latini5, Rui Daniel Prediger4. 1. Laboratório Experimental de Doenças Neurodegenerativas (LEXDON), Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88049-900, Florianópolis, Brazil. aderbal.aguiar@ufsc.br. 2. Laboratório de Bioenergética e Estresse Oxidativo (LABOX), Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88049-900, Florianópolis, Brazil. aderbal.aguiar@ufsc.br. 3. Programa de Pós-Graduação em Neurociências, Universidade Federal de Santa Catarina, Florianópolis, Brazil. aderbal.aguiar@ufsc.br. 4. Laboratório Experimental de Doenças Neurodegenerativas (LEXDON), Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88049-900, Florianópolis, Brazil. 5. Laboratório de Bioenergética e Estresse Oxidativo (LABOX), Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88049-900, Florianópolis, Brazil. 6. INSERM UMR 975 (ex U679), CNRS UMR 7225, Hôpital de la Salpêtrière-Bâtiment, ICM (Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, CRICM), Thérapeutique Expérimentale de la Neurodégénérescence, Université Pierre et Marie Curie (UPMC), 47 Boulevard de l'Hôpital, 75651, Paris, France.
Abstract
INTRODUCTION: Exercise improves the motor symptoms of patients with Parkinson disease in a palliative manner. Existing evidence demonstrates that exercise induces neuroprotection based on the neurotrophic properties. We investigated the effect of exercise on mitochondrial physiology and oxidative stress in an animal model of hemiparkinsonism. METHODS: C57BL/6 mice completed a 6-week exercise program on a treadmill. We injected 6-hydroxydopamine (6-OHDA; 4 μg/2 μl) into the midstriatum. The animals progressively developed bradykinesia and R(-)-apomorphine-induced rotations that were attenuated by exercise. Transcriptional activation of protective genes is mediated by the antioxidant response element (ARE). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) binds to ARE. We investigated the Nrf2-ARE pathway in the striatum of animals. RESULTS: Exercise protected 6-OHDA-induced loss of tyrosine hydroxylase immunolabeling and activated the Nrf2-ARE pathway in the nigrostriatal pathway. Exercise stimulated mitochondrial biogenesis in the striatum of animals that was more resistant to oxidant 6-OHDA and nitric oxide donor (±)-S-nitroso-N-acetylpenicillamine. CONCLUSIONS: In mice, exercise activated Nrf2-ARE signaling in the nigrostriatal pathway that was protective against the development of hemiparkinsonism.
INTRODUCTION: Exercise improves the motor symptoms of patients with Parkinson disease in a palliative manner. Existing evidence demonstrates that exercise induces neuroprotection based on the neurotrophic properties. We investigated the effect of exercise on mitochondrial physiology and oxidative stress in an animal model of hemiparkinsonism. METHODS: C57BL/6 mice completed a 6-week exercise program on a treadmill. We injected 6-hydroxydopamine (6-OHDA; 4 μg/2 μl) into the midstriatum. The animals progressively developed bradykinesia and R(-)-apomorphine-induced rotations that were attenuated by exercise. Transcriptional activation of protective genes is mediated by the antioxidant response element (ARE). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) binds to ARE. We investigated the Nrf2-ARE pathway in the striatum of animals. RESULTS: Exercise protected 6-OHDA-induced loss of tyrosine hydroxylase immunolabeling and activated the Nrf2-ARE pathway in the nigrostriatal pathway. Exercise stimulated mitochondrial biogenesis in the striatum of animals that was more resistant to oxidant 6-OHDA and nitric oxidedonor (±)-S-nitroso-N-acetylpenicillamine. CONCLUSIONS: In mice, exercise activated Nrf2-ARE signaling in the nigrostriatal pathway that was protective against the development of hemiparkinsonism.
Authors: Aderbal S Aguiar; Samantha C Lopes; Fabrine S M Tristão; Daniel Rial; Gisele de Oliveira; Cláudio da Cunha; Rita Raisman-Vozari; Rui D Prediger Journal: Neurotox Res Date: 2016-01 Impact factor: 3.911
Authors: Priscila S Souza; Elaine D Gonçalves; Giulia S Pedroso; Hemelin R Farias; Stella C Junqueira; Rodrigo Marcon; Talita Tuon; Maíra Cola; Paulo C L Silveira; Adair R Santos; João B Calixto; Cláudio T Souza; Ricardo A de Pinho; Rafael C Dutra Journal: Mol Neurobiol Date: 2016-07-22 Impact factor: 5.590