publication

The effects of prolonged stress exposure on the brain of rats and insights to understand the impact of work-related stress on caregivers

Jean Marc Pujo 1, Dewi Yunia Fitriani # 2 3 4, Hajer Ben Saad # 5, Marwa Ghariani # 5 6, Amel Dghim 5, Manel Mellouli 7, Antoine Burin 1, Remi Mutricy 1, Stephanie Houcke 8, Ariane Roujansky 8, Muchtaruddin Mansyur 2 3 4, Flaubert Nkontcho 9, Bertrand de Toffol 10, Ibtissem Ben Amara # 5, Hatem Kallel # 8 11

Affiliations
1 Emergency Department, Cayenne General Hospital, Cayenne, French Guiana.
2 Community Medicine Department, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.
3 Occupational Medicine Specialist Program, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
4 Occupational and Environmental Health Research Center, IMERI, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
5 Laboratory of Medicinal and Environment Chemistry, Higher Institute of Biotechnology, University of Sfax, Sfax, Tunisia.
6 Laboratory of Molecular and Cellular Screening Processes (LPCMC), LR15CBS07, Center of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia.
7 Laboratory of Anatomopathology, CHU Habib Bourguiba, University of Sfax, Sfax, Tunisia.
8 Intensive Care Unit, Cayenne General Hospital, Cayenne, French Guiana.
9 Pharmacy Department, Cayenne General Hospital, Cayenne, French Guiana.
10 Neurology Department, Cayenne General Hospital, Cayenne, French Guiana.
11 Tropical Biome and Immunopathology CNRS UMR-9017, Inserm U 1019, Université de Guyane, Cayenne, French Guiana.
#Contributed equally.

PMID: 38098499
PMCID: PMC10720043
DOI: 10.3389/fnbeh.2023.1288814

Abstract
Introduction: Stress exposure is a significant concern in the healthcare sector. This animal model study aims to reproduce caregivers’ working conditions and determine their impact on the brain.

Method: Twenty-four healthy male rats of the Wistar strain were divided into four groups. Three groups were submitted each to one stressor for 21 days, while the fourth group was used as a control. Stressors were food and water deprivation (FW), permanent illumination (PI), and forced swimming (FS). At the end of the experiment, rats were euthanized, and stress biomarkers, biological parameters, and DNA damage were measured.

Results: Prooxidant biomarker rates increased in the different groups (+50 to +75%) compared to the control (p < 0.0001). Urinary corticosterone rates increased in all stressed animals, mainly in the PI group, with changes of up to +50% compared to the control group. Acetylcholinesterase levels decreased to -50% (p < 0.0001 for the three exposed groups). Total ATPase, (Na+/K+)-ATPase, and Mg2+-ATPase activities decreased in all stressed groups. The percentage of brain cell congestion and apoptosis was 3% for the FW group (p < 0.0001), 2% for the PI group (p < 0.0001), and 4% for the FS group (p < 0.0001) compared to the control (0.8%). DNA damage was observed in all exposed groups. Finally, we noticed behavioral changes and a depression-like syndrome in all stressed rats. Conclusion: Stressful conditions such as the working environment of caregivers can trigger several pathophysiological processes leading to oxidative, neurochemical, and hypothalamic-pituitary-adrenal disorders. These changes can progress to cell damage and apoptosis in the brain and trigger psychological and physical disorders.

Keywords: acetylcholine; apoptosis; brain damage; corticosterone; healthcare; oxidative stress; stress.