Moderate-Intensity Physical Exercise Protects Against Experimental 6-Hydroxydopamine-Induced Hemiparkinsonism Through Nrf2-Antioxidant Response Element Pathway.
BACKGROUND
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.
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.|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.|Programa de Pós-Graduação em Neurociências, Universidade Federal de Santa Catarina, Florianópolis, Brazil. aderbal.aguiar@ufsc.br.
Aderbal Silva
http://orcid.org/0000-0002-6825-3333
AS
Aguiar
Laboratório Experimental de Doenças Neurodegenerativas (LEXDON), Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88049-900, Florianópolis, Brazil.
Marcelo
M
Duzzioni
Laboratório de Bioenergética e Estresse Oxidativo (LABOX), Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88049-900, Florianópolis, Brazil.
Aline Pertile
AP
Remor
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.
Fabrine Sales Massafera
FS
Tristão
Laboratório Experimental de Doenças Neurodegenerativas (LEXDON), Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88049-900, Florianópolis, Brazil.
Filipe C
FC
Matheus
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.
Rita
R
Raisman-Vozari
Laboratório de Bioenergética e Estresse Oxidativo (LABOX), Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88049-900, Florianópolis, Brazil.
Alexandra
A
Latini
Laboratório Experimental de Doenças Neurodegenerativas (LEXDON), Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88049-900, Florianópolis, Brazil.
Rui Daniel
RD
Prediger
D000818:Animals; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D010805:Physical Conditioning, Animal
D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D016627:Oxidopamine
6-OHDA; Exercise; Mitochondria; Neuroprotection; Nrf2/ARE; Parkinson’s disease