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The Impact of Short and Long-Term Exercise on the Expression of Arc and AMPARs During Evolution of the 6-Hydroxy-Dopamine Animal Model of Parkinson’s Disease

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Abstract

The loss of nigral dopaminergic neurons typical in Parkinson’s disease (PD) is responsible for hyperexcitability of medium spiny neurons resulting in abnormal corticostriatal glutamatergic synaptic drive. Considering the neuroprotective effect of exercise, the changes promoted by exercise on AMPA-type glutamate receptors (AMPARs), and the role of activity-regulated cytoskeleton-associated protein (Arc) in the AMPARs trafficking, we studied the impact of short and long-term treadmill exercise during evolution of the unilateral 6-hydroxy-dopamine (6-OHDA) animal model of PD. Wistar rats were divided into sedentary and exercised groups, with and without lesion by 6-OHDA and followed up to 4 months. The exercised groups were subjected to a moderate treadmill exercise 3×/week. We measured the proteins tyrosine hydroxylase (TH), Arc, GluA1, and GluA2/3 in the striatum, substantia nigra, and motor cortex. Our results showed a higher reduction of TH expression in all sedentary groups when compared to all exercised groups in striatum and substantia nigra. In general, larger changes occurred in the striatum in the first and third months after training. After 1 month of exercise, there was significant increase of GluA2/3 with concomitant reduction of GluA1 and Arc. As a balanced system, these changes were reversed in the third month, showing an increase of Arc and GluA1 and decrease of GluA2/3. Similar results for GluAs and Arc were observed in the motor cortex of the exercised animals. These modifications may be relevant for corticostriatal circuits in PD, since the exercise-dependent plasticity can modulate GluAs expression and maybe neuronal excitability.

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Acknowledgements

This study was supported by FAPESP, CAPES, University of São Paulo—NAPNA and CNPq (Brazil). Thanks are also due to Adilson S. Alves for technical assistance and Fernanda Crunfli for helpful comments in relation to data analysis. PCG was the recipient of a fellowship from CAPES, and CCR was the recipient of a fellowship from FAPESP.

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

    P. C. Garcia, C.C. Real & L.R. Britto

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  1. P. C. Garcia
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  2. C.C. Real
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  3. L.R. Britto
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Correspondence to P. C. Garcia.

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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 113/2012).

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Garcia, P.C., Real, C. & Britto, L. The Impact of Short and Long-Term Exercise on the Expression of Arc and AMPARs During Evolution of the 6-Hydroxy-Dopamine Animal Model of Parkinson’s Disease. J Mol Neurosci 61, 542–552 (2017). https://doi.org/10.1007/s12031-017-0896-y

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