Browsing by Author "Van Wyk, Minette"

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    Establishing and validating an in vivo rodent model of chronic restraint stress
    (Stellenbosch : Stellenbosch University, 2022-12) Van Wyk, Minette; Essop, M. Faadiel; Joseph, Danzil; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
    ENGLISH ABSTRACT: Introduction. Psychological stress has emerged as one of the health epidemics of the 21st century and provides an impetus for increased investigation into the effects of a dysregulated stress response on whole body physiology. Although previous studies helped to clarify the association between chronic psychological stress and the onset and progression of cardiovascular diseases, a paucity of mechanistic insights underlying this association remain. Considering the complex nature of the stress system and the similarities that exist between humans and animals, it is therefore ideal to use rodent models to investigate stress-related disorders. Although the incidence and onset of various disorders in humans are gender-specific, clinical, and preclinical research using male subjects still far outnumber those using females. This study therefore aimed to establish and validate an in vivo model of chronic restraint stress in male and female Wistar rats. Materials and Methods. Male and female Wistar rats were subjected to a 4-week restraint stress protocol versus matched controls. Following this, behavioral tests (elevated plus maze [EPM] and tail flick task) were performed together with an assessment of body weight changes and biochemical biomarkers to ascertain whether the model was successfully established. Results & Findings. Our data revealed that male stressed rats displayed a decreased percentage change in body weight over time versus controls (p<0.01). Furthermore, the male stressed group exhibited increased plasma corticosterone levels compared to controls (p<0.01), while no significant differences were detected for plasma adrenocorticotropic hormone (ACTH) concentrations. Male brain-derived neurotrophic factor levels (biomarker for neuronal survival and growth) were lower in the stress group versus controls (p<0.05). Stressed males also displayed a reduced number of attempts into the open arms of the EPM versus controls (p<0.05). There were no significant weight changes for female rats. However, stressed females exhibited lowered plasma corticosterone levels versus controls (p<0.05), while also displaying higher plasma ACTH concentrations compared to the control group (p<0.05). Stressed females also displayed increased rears (as assessed by EPM test) versus matched controls (p<0.01). Our findings reveal intriguing sex-based differences in response to a chronic restraint stress protocol, with males displaying a depressive-type phenotype while females exhibited a post-traumatic stress disorder phenotype. Sex-specific preclinical research can provide unique insights into the various mechanisms driving stress-related diseases and should eventually lead to the identification of novel diagnostic and therapeutic targets.