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Establishing and validating an in vivo rodent model of chronic restraint stress
Thesis (MSc)--Stellenbosch University, 2022.
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| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2022
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| _version_ | 1867613844720844800 |
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| access_status_str | Open Access |
| author | Van Wyk, Minette |
| author2 | Essop, M. Faadiel |
| author_browse | Essop, M. Faadiel Van Wyk, Minette |
| author_facet | Essop, M. Faadiel Van Wyk, Minette |
| author_sort | Van Wyk, Minette |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MSc)--Stellenbosch University, 2022. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/126118 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:42:35.472Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2022 |
| publishDateRange | 2022 |
| publishDateSort | 2022 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/126118 Establishing and validating an in vivo rodent model of chronic restraint stress Van Wyk, Minette Essop, M. Faadiel Joseph, Danzil Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences. Wistar rats In vivo models Wistar rats -- Effect of stress on Stress (Psychology) -- Animal models UCTD Thesis (MSc)--Stellenbosch University, 2022. 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. AFRIKAANSE OPSOMMING: Inleiding. Chroniese spanning kom tans na vore as die gesondheid epidemie van die 21ste eeu en lei tot ‘n toename in navorsing oor die implikasies van 'n chroniese stres reaksie op die hele liggaam se fisiologie. Vorige studies het gehelp om die verwantskap tussen chroniese spanning en die aanvang en bevordering van kardiovaskulêre siektes te verduidelik. Daar is egter steeds onvoldoende kennis oor die onderliggende meganismes wat hierdie verwantskap verduidelik. Inaggenome die kompleksiteit van die stres sisteem en die ooreenkomste wat tussen mense en diere bestaan, is dit ideaal om knaagdier modelle te gebruik om stres verwante kondisies te ondersoek. Alhoewel die voorkoms en aanvang van verskeie kondisies in mense geslag spesifiek is, gebruik navorsing steeds beduidend meer manlike as vroulike deelnemers. Hierdie studie het dus ten doel gehad om 'n in vivo model van chroniese beperkings stres in Wistar-rotte te vestig. Materiale en Metodes. Manlike en vroulike Wistar-rotte is gedurende die studie gebruik. Die eksperimentele groep is blootgestel aan 'n inperkings stres-protokol van vier weke. Gedragstoetse (verhoogde plus doolhof [EPM] en stert wip toets) is hierna uitgevoer tesame met assessering van liggaamsgewig en plasma merkers, om sodoende vas te stel of die model suksesvol gevestig is. Resultate en bevindinge. Ons data dui aan dat manlike rotte wat aan die stres-protokol blootgestel is, ‘n kleiner persentasie in gewigstoename teenoor die kontrole groep getoon het (p<0.01). Verder het die manlike stres groep verhoogde plasma kortikosteroon vlakke getoon in vergelyking met die kontroles (p<0.01), terwyl geen beduidende verskille vir plasma adrenokortikotropiese hormoon (ACTH) konsentrasies gevind is nie. Manlike brein-vervaardigde neurotrofiese faktor vlakke (merker vir neurale oorlewing en groei) was laer in die stres groep teenoor die kontroles (p<0.05). In vergelyking met die kontrole groep, het die mannetjies wat aan die stres-protokol blootgestel is ‘n vermindering in die aantal pogings getoon met betrekking tot die oop arms van die EPM (p<0.05). Daar was geen betekenisvolle veranderinge in gewig vir die vroulike rotte nie. Verlaagde plasma kortikosteroon vlakke is in die vroulike stres groep opgemerk in vergelyking met die kontroles (p<0.05), terwyl hulle ook hoër plasma ACTH-konsentrasies teenoor die kontrolegroep (p<0.05) getoon het. Wyfies blootgestel aan die stres-protokol het meer male op hul agterpote gestaan (soos geassesseer deur EPM-toets) in teenstelling met die kontroles (p<0.01). Ons bevindinge onthul interessante geslags gebaseerde verskille in reaksie op 'n chroniese inperkings stres-protokol. Hier, het mannetjies 'n depressiewe fenotipe getoon terwyl wyfies 'n post traumatiese stresversteuring-fenotipe getoon het. Geslag spesifieke navorsing met diere kan unieke insigte verskaf met betrekking tot die verskeie meganismes wat spannings verwante kondisies en siektes bevorder. Dit behoort aanvullend te lei tot die identifisering van nuwe diagnostiese en terapeutiese teikens. Masters 2022-11-21T08:51:37Z 2023-01-16T12:51:00Z 2022-11-21T08:51:37Z 2023-01-16T12:51:00Z 2022-12 Thesis http://hdl.handle.net/10019.1/126118 en_ZA Stellenbosch University xxiii, 88 pages : illustrations (some color) application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Wistar rats In vivo models Wistar rats -- Effect of stress on Stress (Psychology) -- Animal models UCTD Van Wyk, Minette Establishing and validating an in vivo rodent model of chronic restraint stress |
| title | Establishing and validating an in vivo rodent model of chronic restraint stress |
| title_full | Establishing and validating an in vivo rodent model of chronic restraint stress |
| title_fullStr | Establishing and validating an in vivo rodent model of chronic restraint stress |
| title_full_unstemmed | Establishing and validating an in vivo rodent model of chronic restraint stress |
| title_short | Establishing and validating an in vivo rodent model of chronic restraint stress |
| title_sort | establishing and validating an in vivo rodent model of chronic restraint stress |
| topic | Wistar rats In vivo models Wistar rats -- Effect of stress on Stress (Psychology) -- Animal models UCTD |
| url | http://hdl.handle.net/10019.1/126118 |
| work_keys_str_mv | AT vanwykminette establishingandvalidatinganinvivorodentmodelofchronicrestraintstress |