Moderate-Intensity Physical Exercise Protects Against Experimental 6-Hydroxydopamine-Induced Hemiparkinsonism Through Nrf2-Antioxidant Response Element Pathway.

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.

• Authors: Aderbal Silva Aguiar Jr, Marcelo Duzzioni, Aline Pertile Remor, Fabrine Sales Massafera Tristão, Filipe C Matheus, Rita Raisman-Vozari, Alexandra Latini, Rui Daniel Prediger
• Journal: Neurochemical research (Neurochem Res) Vol. 41 Issue 1-2 Pg. 64-72 (Feb 2016) ISSN: 1573-6903 [Electronic] United States
• PMID: 26323504 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• Oxidopamine

Topics

• Animals
• Male
• Mice
• Mice, Inbred C57BL
• NF-E2-Related Factor 2 (metabolism)
• Oxidopamine (toxicity)
• Parkinsonian Disorders (etiology, metabolism, prevention & control)
• Physical Conditioning, Animal