Department of Physiological Sciences

Permanent URI for this community

https://scholar.sun.ac.za/handle/10019.1/232

Browse

Browsing Department of Physiological Sciences by Author "Benecke, Rohan Meerholz"

Now showing 1 - 1 of 1
  • Thumbnail Image
    Item
    Comparative assessment of neurological vs metabolic allostasis as reflected in human skin fibroblasts
    (Stellenbosch : Stellenbosch University, 2022-12) Benecke, Rohan Meerholz; Smith, Carine; Van de Vyver, Mari; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
    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.