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Advanced Neurology

ORIGINAL RESEARCH ARTICLE
Unpredictable mild stress accelerates the

emergence of motor deficits in a rat model of
progressive parkinsonism

Laura F. M. Olivatto 1† , Debora M. G. Cunha 1† , Leonardo B. Silva 1 ,
Alvaro C. Lima 1 , Marcela Becegato 1 , Vinicius S. Bioni 1 ,
1
Raphael Wuo-Silva 2 , Deborah Suchecki 3 , and Regina H. Silva *
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

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
† These authors contributed equally remains poorly understood. This study aimed to investigate the effects of exposure
to this work. to a chronic unpredictable mild stress (UMS) protocol on the onset of parkinsonism
*Corresponding author: in Wistar rats repeatedly treated with a low dose of reserpine. Wistar rats were
Regina H. Silva either exposed to UMS for 1 week or not exposed (control group). Then, the animals
(r.silva@unifesp.br)
were repeatedly treated with a low dose of reserpine or vehicle every other day for
Citation: Olivatto LFM, 20 days. Behavioral motor evaluations were conducted using catalepsy and open
Cunha DMG, Silva LB, et al. field tests. Moreover, plasma corticosterone (CORT) levels and lipid peroxidation
Unpredictable mild stress
accelerates the emergence of motor were evaluated. As expected, the UMS protocol increased plasma CORT levels,
deficits in a rat model of progressive and reserpine treatment led to a progressive enhancement of cataleptic behavior.
parkinsonism. Adv Neurol. Animals exposed to UMS and treated with reserpine exhibited motor alteration
2024;3(4):4037.
doi: 10.36922/an.4037 earlier during the protocol. No differences were observed in oxidative stress between
experimental and control groups, as evaluated through lipid peroxidation assay. Our
Received: June 28, 2024
results showed that chronic mild stress accelerated the onset of motor deficits in
Accepted: October 29, 2024 reserpine-treated animals.
Published Online: November 19,
2024
Keywords: Oxidative stress; Corticosterone; Motor impairment; Parkinson’s disease;
Copyright: © 2024 Author(s). Neurodegeneration
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution
License, permitting distribution,
and reproduction in any medium, 1. Introduction
provided the original work is
properly cited. Parkinson’s disease (PD) is a common neurodegenerative disorder associated with aging.
Publisher’s Note: AccScience It is characterized by the progressive death of dopaminergic neurons in the substantia
Publishing remains neutral with nigra pars compacta (SNpc) and subsequent depletion of dopamine in the striatum.
1
regard to jurisdictional claims in
published maps and institutional This disruption in dopaminergic transmission affects the thalamocortical pathways
2,3
affiliations. involved in the control of voluntary movement, resulting in the development of
Volume 3 Issue 4 (2024) 1 doi: 10.36922/an.4037