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ORIGINAL RESEARCH ARTICLE

Unpredictable mild stress accelerates the emergence of motor deficits in a rat model of progressive parkinsonism

Laura F. M. Olivatto1† ,  Debora M. G. Cunha1† ,  Leonardo B. Silva1 ,  Alvaro C. Lima1 ,  Marcela Becegato1 ,  Vinicius S. Bioni1 ,  Raphael Wuo-Silva2 ,  Deborah Suchecki3 ,  Regina H. Silva1*
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1 Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil
2 Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo, Brazil
3 Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil
Advanced Neurology 2024, 3(4), 4037 https://doi.org/10.36922/an.4037
Submitted: 28 June 2024 | Accepted: 29 October 2024 | Published: 19 November 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Parkinson’s disease (PD) is a multifactorial condition associated with genetic and environmental factors. In recent years, the role of chronic psychophysiological stress as a predisposing factor for PD is gaining increasing attention. Clinical and experimental evidence indicates that chronic stress exerts adverse effects on the brain. Nevertheless, the potential role of chronic stress in the predisposition to PD remains poorly understood. This study aimed to investigate the effects of exposure to a chronic unpredictable mild stress (UMS) protocol on the onset of parkinsonism in Wistar rats repeatedly treated with a low dose of reserpine. Wistar rats were either exposed to UMS for 1 week or not exposed (control group). Then, the animals were repeatedly treated with a low dose of reserpine or vehicle every other day for 20 days. Behavioral motor evaluations were conducted using catalepsy and open field tests. Moreover, plasma corticosterone (CORT) levels and lipid peroxidation were evaluated. As expected, the UMS protocol increased plasma CORT levels, and reserpine treatment led to a progressive enhancement of cataleptic behavior. Animals exposed to UMS and treated with reserpine exhibited motor alteration earlier during the protocol. No differences were observed in oxidative stress between experimental and control groups, as evaluated through lipid peroxidation assay. Our results showed that chronic mild stress accelerated the onset of motor deficits in reserpine-treated animals.

Keywords
Oxidative stress
Corticosterone
Motor impairment
Parkinson’s disease
Neurodegeneration
Funding
This study was financed by Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP (grant 2017/26253-3), and by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/Brasil – CAPES (finance code 001). RHS and DS are recipients of research fellowships from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, grants 313631/2021-2 and 305076/2023-0).
Conflict of interest
The authors declare no conflicts of interest.
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Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
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