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Treadmill Exercise Prevents Increase of Neuroinflammation Markers Involved in the Dopaminergic Damage of the 6-OHDA Parkinson’s Disease Model

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Abstract

Parkinson’s disease (PD) involves loss of dopaminergic neurons in the substantia nigra (SN), which can be correlated to neuroinflammatory changes with the aging of the nervous system. On the other hand, exercise can reduce the deleterious effects promoted by age, but the mechanism involved is still unclear. This study investigated the preventive exercise-induced changes on neuroinflammatory processes in a rat model of PD induced by unilateral striatal injections of 6-hydroxydopamine (6-OHDA). Adult male Wistar rats were divided into two groups: (1) sedentary (SED) or (2) exercised (EX), animals that did treadmill exercise three times per week, every other day, for 4 weeks prior to 6-OHDA or saline injection. The rats were then divided into four sub-groups: (1) sedentary saline (SED), (2) sedentary 6-OHDA (SED + 6-OHDA), (3) exercised saline (EX), and (4) exercised 6-OHDA (EX + 6-OHDA). Seven and 30 days after surgery, brains were collected for immunohistochemistry and immunoblotting for dopaminergic and neuroinflammatory markers into SN and striatum. The SED + 6-OHDA animals presented an increase in the astrocyte, microglial, and oxidative species activation. On the other hand, EX + 6-OHDA animals did not present neuroinflammatory responses and performed better apormorphine test. Our data suggest that treadmill exercise throughout life can markedly reduce the chances of dopamine decrease, reinforcing studies that showed a lower incidence of Parkinson’s disease in patients who were active during life.

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Acknowledgements

This study was supported by The São Paulo Research Foundation (FAPESP, Brazil), Coordination for the Improvement of Higher Education Personnel (CAPES, Brazil), Research Center on Applied Neuroscience (NAPNA, Brazil), and The National Council for Scientific and Technological Development (CNPq, Brazil). Thanks are also due to Adilson S. Alves for the technical assistance, Ellen Claire Ford for the help in some experiments during her undergraduation internship (Minority Health and Health Disparities International Research Training (MHIRT), USA), and Elisa Guimarães-Souza for the grammar review. CCR was the recipient of a fellowship from FAPESP (2008/58716-3), and PCG was the recipient of a fellowship from CAPES.

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Authors and Affiliations

  1. Laboratory of Cellular Neurobiology, Department of Physiology and Biophysics, University of São Paulo, Av Prof Lineu Prestes, 1524, sala 239, São Paulo, SP, 05508-000, Brazil

    Caroline Cristiano Real, Priscila Crespo Garcia & Luiz R. G. Britto

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  1. Caroline Cristiano Real
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  2. Priscila Crespo Garcia
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  3. Luiz R. G. Britto
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Contributions

CCR and LRGB designed the experiments. CCR and PCG collected and analyzed the data and wrote the paper. All the authors discussed the data, edited, commented on the manuscript, and approved the final version of the manuscript.

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Correspondence to Caroline Cristiano Real.

Ethics declarations

The experiments were carried out in accordance with the guidelines of the National Council for the control of Animal Experimentation (CONCEA, Brazil), a constituent body of the Ministry of Science, Technology, and Innovation (MCTI, Brazil). All protocols were approved by the Ethics Committee for Animal Research of the Institute of Biomedical Sciences of the University of São Paulo (CEUA-ICB/USP, Brazil) (protocol number 14/2009).

Conflict of Interest

We wish to confirm that there are no known conflicts of interest associated with this publication and there has been financial support from FAPESP to CCR and from CAPES to PCG. FAPESP and CNPq supported LRGB.

Electronic Supplementary Material

Supplementary Figure 1

Double staining for tyrosine hydroxylase (TH) and neuronal nuclei (NeuN) in the substantia nigra. There is a NeuN and TH decrease in the experimental side of SED + 6-OHDA group indicating that there was neuronal loss, not only TH down-regulation. (GIF 314 kb)

High resolution image (TIFF 13596 kb)

Supplementary Table 1

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Real, C.C., Garcia, P.C. & Britto, L.R.G. Treadmill Exercise Prevents Increase of Neuroinflammation Markers Involved in the Dopaminergic Damage of the 6-OHDA Parkinson’s Disease Model. J Mol Neurosci 63, 36–49 (2017). https://doi.org/10.1007/s12031-017-0955-4

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