Molecular Neurobiology

, Volume 56, Issue 4, pp 2944–2951 | Cite as

Treadmill Exercise Attenuates l-DOPA-Induced Dyskinesia and Increases Striatal Levels of Glial Cell-Derived Neurotrophic Factor (GDNF) in Hemiparkinsonian Mice

  • Ana E. Speck
  • Marissa G. Schamne
  • Aderbal S. AguiarJr
  • Rodrigo A. Cunha
  • Rui D. PredigerEmail author


Exercise can act as a disease-modifying agent in Parkinson’s disease (PD), and we have previously demonstrated that voluntary exercise in running wheels during 2 weeks normalizes striatopallidal dopaminergic signaling and prevents the development of l-DOPA-induced dyskinesia (LID) in C57BL/6 mice. We now tested whether LID in Swiss albino mice could be attenuated by treadmill-controlled exercise alone or in combination with the reference antidyskinetic drug amantadine. The daily intraperitoneal (i.p.) treatment with three different doses of l-DOPA/benserazide (30/12.5, 50/25, or 70/35 mg/kg) during 3 weeks induced increasing levels of LID scores in hemiparkinsonian Swiss albino mice previously lesioned with a unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA, 10 μg). Then, we addressed the antidyskinetic effects of treadmill-controlled exercise by comparing LID, induced by l-DOPA/benserazide (50/25 mg/kg, i.p.) during 4 weeks, in sedentary and daily exercised mice. Exercise reduced LID and improved motor skills of dyskinetic mice, as indicated by decreased contralateral bias, increase in maximal load test, and latency to fall in rotarod. The antidyskinetic effect of amantadine (60 mg/kg, i.p.) was only observed in sedentary mice, indicating the absence of synergistic antidyskinetic effect of the combination of treadmill exercise plus amantadine. Finally, Western blot analysis unraveled an ability of exercise to increase the striatal immunocontent of glial cell-derived neurotrophic factor (GDNF), apart from normalizing striatal levels of tyrosine hydroxylase. These findings show that controlled treadmill exercise attenuates LID and provide the first indication that the antidyskinetic effects of treadmill exercise may involve increased striatal GDNF levels.


Exercise Treadmill Dyskinesia l-DOPA GDNF Parkinson’s disease 6-OHDA 


Funding Information

This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Universal 408676/2016-7), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-FCT), Programa de Apoio aos Núcleos de Excelência (PRONEX-Project NENASC), and Fundação de Apoio à Pesquisa do Estado de Santa Catarina (FAPESC). MS received scholarships from CNPq, and AES received scholarship from FAPESC/CAPES. ASA and RDP are supported by research fellowships from CNPq.

Compliance with Ethical Standards

All experimental protocols were approved by the Institutional Animal Care and Use Committee (IACUC) of UFSC (protocol PP00357).

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12035_2018_1278_MOESM1_ESM.wmv (7.2 mb)
ESM 1 (WMV 7410 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Graduate Program of Neuroscience, Center of Biological SciencesFederal University of Santa Catarina (UFSC)FlorianópolisBrazil
  2. 2.Department of Pharmacology, Center of Biological SciencesFederal University of Santa Catarina (UFSC)FlorianópolisBrazil
  3. 3.Research Group on Biology of Exercise, Department of Health SciencesFederal University of Santa Catarina (UFSC)AraranguáBrazil
  4. 4.CNC - Center for Neuroscience and Cell BiologyUniversity of CoimbraCoimbraPortugal
  5. 5.Faculty of MedicineUniversity of CoimbraCoimbraPortugal

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