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Exercise Improves Cognitive Impairment and Dopamine Metabolism in MPTP-Treated Mice

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Abstract

The classical motor symptoms of Parkinson’s disease (PD) are preceded by non-motor symptoms in preclinical stages, including cognition impairment. The current drug treatment for PD is palliative and does not meet the clinical challenges of the disease, such as levodopa-induced dyskinesia, non-motor symptoms, and neuroprotection. We investigated the neuroprotective and disease-modifying potential of physical exercise in a preclinical animal model of PD. C57BL/6 mice (adult males) ran on a horizontal treadmill for 6 weeks (moderate intensity, 5 times/week) and were treated intranasally with 65 mg/kg of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Exercise did not protect against MPTP-induced nigrostriatal neurodegeneration or frontostriatal dopamine depletion but decreased striatal dopamine turnover. Exercise also attenuated procedural and working memory impairment and D2 receptor hypersensitivity in MPTP-treated mice. In summary, exercise improved dopaminergic neurotransmission and enhanced cognition in a preclinical animal model of PD.

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Acknowledgments

The authors are appreciative for the financial support and grants provided by the Brazilian agencies Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), CAPES-COFECUB (France/Brazil; 681/2010), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Fundação de Apoio à Pesquisa Científica e Tecnológica do Estado de Santa Catarina (FAPESC). The funders had no role in study design, data collection and analysis, the decision to publish, or preparation of the manuscript. The authors have no financial or personal conflicts of interest related to this study.

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Authors and Affiliations

  1. Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, SC, 88040-900, Brazil

    Aderbal S. Aguiar Jr., Samantha C. Lopes & Daniel Rial

  2. Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, 88040-900, Brazil

    Aderbal S. Aguiar Jr. & Rui D. Prediger

  3. INSERM UMR 975 – CNRS UMR 7225, Hôpital de la Salpêtrière—Bâtiment, Centre de Recherche de l’Institut du Cerveau et de la Moelle épinière, Université Pierre et Marie Curie, UPMC, 75651, Paris, France

    Fabrine S. M. Tristão & Rita Raisman-Vozari

  4. Departamento de Farmacologia, Centro Politécnico, Universidade Federal do Paraná, Curitiba, PR, 81531-980, Brazil

    Gisele de Oliveira & Cláudio da Cunha

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  1. Aderbal S. Aguiar Jr.
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  2. Samantha C. Lopes
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  3. Fabrine S. M. Tristão
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  8. Rui D. Prediger
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Correspondence to Aderbal S. Aguiar Jr..

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12640_2015_9566_MOESM1_ESM.tif

Fig. S1–Degradation of DA in the prefrontal cortex and striatum of mice, as indicated by the DOPAC/DA ratio. MPTP increased striatal DA metabolism. Exercise decreased DA metabolism in the striatum and prefrontal cortex. Values are mean ± standard error. * P < 0.05 vs. sal. # P < 0.05 vs. sed. Abbreviations: DA, dopamine; DOPAC, 3,4-dihydroxyphenylacetic acid; exe, exercise; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; sed, sedentary; sal, saline (TIFF 483 kb)

12640_2015_9566_MOESM2_ESM.tif

Fig. S2–Maximum catalepsy severity after administering mice a high dose of haloperidol (1.0 mg/kg). Abbreviations: exe, exercise; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; sed, sedentary; sal, saline (TIFF 292 kb)

12640_2015_9566_MOESM3_ESM.docx

Table S1–* P < 0.05 vs. respective saline control. Abbreviations: exe, exercise; DHPG, dihydroxyphenylglycol; DOPAC, 3,4-dihydroxyphenylacetic acid; HVA, homovanillic acid; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; PFC, prefrontal cortex; 5-HIAA, 5-hydroxyindoleacetic acid; sed, sedentary; sal, saline (DOCX 16 kb)

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Aguiar, A.S., Lopes, S.C., Tristão, F.S.M. et al. Exercise Improves Cognitive Impairment and Dopamine Metabolism in MPTP-Treated Mice. Neurotox Res 29, 118–125 (2016). https://doi.org/10.1007/s12640-015-9566-4

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