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Comparative assessment of neurological vs metabolic allostasis as reflected in human skin fibroblasts
Thesis (PhD)--Stellenbosch University, 2022.
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| Format: | Thesis |
| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2022
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| _version_ | 1867613799032291328 |
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| access_status_str | Open Access |
| author | Benecke, Rohan Meerholz |
| author2 | Smith, Carine |
| author_browse | Benecke, Rohan Meerholz Smith, Carine |
| author_facet | Smith, Carine Benecke, Rohan Meerholz |
| author_sort | Benecke, Rohan Meerholz |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (PhD)--Stellenbosch University, 2022. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/125918 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:41:52.972Z |
| 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:10019.1/125918 Comparative assessment of neurological vs metabolic allostasis as reflected in human skin fibroblasts Benecke, Rohan Meerholz Smith, Carine Van de Vyver, Mari Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences. Allostasis Fibroblasts Post-traumatic stress disorder (PTSD) -- Diagnosis Mental health -- Genetic aspects Fibroblast growth factors UCTD Thesis (PhD)--Stellenbosch University, 2022. ENGLISH ABSTRACT: Incidence of mental health disorders are rising in modernity. Many mental health disorders share molecular and genetic overlap as well as having high incidence of comorbidities. Stress and the compounded effect of multiple low-grade stressors may be contributing to a relative increase in the pro-inflammatory and oxidative state seen in mental health disorders and other complex diseases. This leads to allostatic changes that potentially contribute to disease aetiology and progression. Allostasis is the process of homeostatic equilibrium under stress. Inflammation, which is often used to measure allostatic load, is potentially the incorrect measure as inflammation is transient and the damage ascribed to chronic inflammation is due to increases in reactive oxygen species (ROS) and decreases in antioxidant capacity. Post-traumatic stress disorder (PTSD) is a mental health disorder that is characterised by severe stressors and a maladaptive response to these stressors. Although the role of inflammation and oxidative stress have been implicated in the disease aetiology it is still a relatively neglected aspect of PTSD research. Furthermore, despite the high rate of comorbidities associated with PTSD there is still a lack of understanding in terms of the peripheral effects of PTSD. PTSD and potentially comorbid obesity, present ideal health paradigms to assess this relative neglect of allostatic changes, in particular those in the periphery, that may be contributing to disease outcome in PTSD. A novel therapeutic target, namely the trace amine system, is investigated as a potential anxiolytic in zebrafish larvae that could address allostatic changes of chronic diseases such as PTSD and obesity. Patient derived fibroblasts are used as model cell type to investigate potential functional changes in the periphery of PTSD patients as result of allostatic load. Finally, the potential for peripheral signalling to influence central function is explored in astrocytes, that represent the ideal candidate cell to investigate allostatic load in the context of mental health. Changes in peripheral calcium function and central redox function indicate the allostatic load of PTSD can modulate the chemiosmotic potential of cells through longitudinal shifts in the homeostatic set point. As a result, low grade cumulative stressors may be damaging to cellular function without activating endogenous defence mechanisms. AFRIKAANSE OPSOMMING: Die voorkoms van geestesgesondheidsversteurings neem toe in moderniteit. Baie geestesgesondheidsversteurings deel molekulêre en genetiese oorvleueling sowel as 'n hoë voorkoms van komorbiditeite. Stres en die saamgestelde effek van verskeie laegraadse stressors kan bydra tot 'n relatiewe toename in die pro-inflammatoriese en oksidatiewe toestand wat in geestesgesondheidsversteurings en ander komplekse siektes gesien word. Dit lei tot allostatiese veranderinge wat potensieel bydra tot siekte-etiologie en progressie. Inflammasie, wat dikwels gebruik word om allostatiese lading te meet, is potensieel die verkeerde maatstaaf vir hierdie mate, aangesien inflammasie verbygaande is en die skade wat aan chroniese inflammasie toegeskryf word, te wyte is aan toenames in ROS en afname in antioksidantkapasiteit. PTSV is 'n geestesgesondheidsversteuring wat gekenmerk word deur ernstige stressors en 'n wanadaptiewe reaksie op hierdie stressors. Alhoewel die rol van inflammasie en oksidatiewe stres by die siekte- etiologie van PTSV betrokke is, is dit steeds 'n relatief verwaarloosde aspek van PTSV-navorsing. Verder, ten spyte van die hoë koers as komorbiditeite wat verband hou met PTSV, is daar steeds 'n gebrek aan begrip in terme van die perifere effekte van PTSV. PTSV en potensieel komorbiede vetsug, bied ideale gesondheidsparadigmas aan om hierdie relatiewe verwaarlosing van allostatiese veranderinge te evalueer, veral dié in die periferie, wat kan bydra tot siekte-uitkoms in PTSV. 'n Nuwe terapeutiese teiken, naamlik die spooramienstelsel, word ondersoek as 'n potensiële angsverliggingsmiddel in sebravislarwes wat ook moontlik allostatiese veranderinge van chroniese siektes soos PTSV en vetsug kan aanspreek. Ten slotte word die potensiaal vir perifere sein om sentrale funksie te beïnvloed, in astrosiete ondersoek, wat die ideale kandidaatsel verteenwoordig om allostatiese lading in die konteks van geestesgesondheid te ondersoek. Veranderinge in perifere kalsiumfunksie en sentrale redoksfunksie dui aan dat die allostatiese lading van PTSV die chemiosmotiese potensiaal van selle kan moduleer deur longitudinale verskuiwings in die homeostatiese stelpunt.As gevolg hiervan kan laegraad kumulatiewe stressors skadelik wees vir sellulêre funksie sonder om endogene verdedigingsmeganismes te aktiveer. Doctoral 2022-10-20T18:56:32Z 2023-01-16T12:41:15Z 2022-10-20T18:56:32Z 2023-01-16T12:41:15Z 2022-12 Thesis http://hdl.handle.net/10019.1/125918 en_ZA Stellenbosch University iv, 118 pages : illustrations (some color) application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Allostasis Fibroblasts Post-traumatic stress disorder (PTSD) -- Diagnosis Mental health -- Genetic aspects Fibroblast growth factors UCTD Benecke, Rohan Meerholz Comparative assessment of neurological vs metabolic allostasis as reflected in human skin fibroblasts |
| title | Comparative assessment of neurological vs metabolic allostasis as reflected in human skin fibroblasts |
| title_full | Comparative assessment of neurological vs metabolic allostasis as reflected in human skin fibroblasts |
| title_fullStr | Comparative assessment of neurological vs metabolic allostasis as reflected in human skin fibroblasts |
| title_full_unstemmed | Comparative assessment of neurological vs metabolic allostasis as reflected in human skin fibroblasts |
| title_short | Comparative assessment of neurological vs metabolic allostasis as reflected in human skin fibroblasts |
| title_sort | comparative assessment of neurological vs metabolic allostasis as reflected in human skin fibroblasts |
| topic | Allostasis Fibroblasts Post-traumatic stress disorder (PTSD) -- Diagnosis Mental health -- Genetic aspects Fibroblast growth factors UCTD |
| url | http://hdl.handle.net/10019.1/125918 |
| work_keys_str_mv | AT beneckerohanmeerholz comparativeassessmentofneurologicalvsmetabolicallostasisasreflectedinhumanskinfibroblasts |