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Sleep deprivation induces late deleterious effects in a pharmacological model of Parkinsonism

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Abstract

Parkinson’s disease is a degenerative, chronic and progressive disease, characterized by motor dysfunctions. Patients also exhibit non-motor symptoms, such as affective and sleep disorders. Sleep disorders can potentiate clinical and neuropathological features and lead to worse prognosis. The goal of this study was to evaluate the effects of sleep deprivation (SD) in mice submitted to a progressive pharmacological model of Parkinsonism (chronic administration with a low dose of reserpine). Male Swiss mice received 20 injections of reserpine (0.1 mg/kg) or vehicle, on alternate days. SD was applied before or during reserpine treatment and was performed by gentle handling for 6 h per day for 10 consecutive days. Animals were submitted to motor and non-motor behavioral assessments and neurochemical evaluations. Locomotion was increased by SD and decreased by reserpine treatment. SD during treatment delayed the onset of catalepsy, but SD prior to treatment potentiated reserpine-induced catalepsy. Thus, although SD induced an apparent beneficial effect on motor parameters, a delayed deleterious effect on alterations induced by reserpine was found. In the object recognition test, both SD and reserpine treatment produced cognitive deficits. In addition, the association between SD and reserpine induced anhedonic-like behavior. Finally, an increase in oxidative stress was found in hippocampus of mice subjected to SD, and tyrosine hydroxylase immunoreactivity was reduced in substantia nigra of reserpine-treated animals. Results point to a possible late effect of SD, aggravating the deficits in mice submitted to the reserpine progressive model of PD.

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Acknowledgements

The authors would like to thank Claudenice M. dos Santos and Cleomar S. Ferreira (in memoriam) for technical assistance. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES, Finance Code 001) and by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Grants 2015/03354-3 and 2017/26253-3). RHS is a recipient of a research fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Grant 313631/2021-2).

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  1. Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo (EPM/UNIFESP), Rua Botucatu, 862, Ed. Leal Prado, São Paulo, Brazil

    L. B. Lopes-Silva, D. M. G. Cunha, A. C. Lima, V. S. Bioni, N. Gonçalves, J. P. F. Kurita, R. Wuo-Silva & R. H. Silva

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  1. L. B. Lopes-Silva
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  2. D. M. G. Cunha
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  3. A. C. Lima
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  5. N. Gonçalves
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  6. J. P. F. Kurita
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Correspondence to R. H. Silva.

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Lopes-Silva, L.B., Cunha, D.M.G., Lima, A.C. et al. Sleep deprivation induces late deleterious effects in a pharmacological model of Parkinsonism. Exp Brain Res (2024). https://doi.org/10.1007/s00221-024-06811-0

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