Investigating the neuroprotective effect of exercise; the role of redox homeostasis

Fisher Dr, Emily ORCID: 0000-0002-7015-7738 (2021). Investigating the neuroprotective effect of exercise; the role of redox homeostasis. University of Birmingham. Ph.D.

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The balance between oxidant production and the antioxidant defence system is essential to brain health. First-episode psychosis (FEP) and schizophrenia (SZ) are psychiatric disorders that affect the patients’ contact with reality, with unique presentation of symptoms and experiences. Both FEP and SZ can be characterised by perturbed redox status, notably via antioxidant depletion. Previous research, undertaken in healthy populations, has highlighted the ability of exercise training to regulate redox balance.
One particular biomarker of redox status is the antioxidant glutathione (GSH), which has a principal role of removing toxic substances from the cell, especially in the brain.
This thesis presents novel data investigating the drawbacks of exercise study design in youth mental health, the efficacy of a training intervention in ‘normalising’ measures of antioxidant capacity, oxidative stress, inflammation and functionality in FEP. Studies presented go on to interrogate some of the redox-related mechanisms of the neurodevelopmental aspect of psychosis pathophysiology. Assessment of GSH in the brain, blood and in patient-derived cell models offers significant gateways into elucidating the pathological mechanisms of mental ill-health.
In order to address some of the principle weaknesses in previous study design which have aimed to provide exercise to a FEP cohort, chapter 2 of this thesis used personalised heart rate zones (50-70% VO2max) to standardise bouts of activity across a range of exercise modalities, in a healthy but sedentary group of young people. The study was successful in provoking a redox response
during each acute bout, which typically initiates the stimulation of adaptive processes. This study achieved 100% retention, which also demonstrated that engagement in an exercise intervention is possible in a sedentary group, when choice of activity and variety of exercise mode are offered to the participant. Chapters 3 and 4 highlight the therapeutic benefits of regular exercise training (12 weeks, 3-4 times/week, 40-60 minutes) for FEP patients in a randomised trial. The study highlighted the positive impact of increased physical activity on peripheral and brain indices of GSH, markers of oxidative stress, and patient- centred measures of psychotic symptomology and daily function. In a more in- depth assessment of the GSH cycle and indices of cell damage, chapter 5 describes the characterisation and generation of mature astrocytes and neurons from SZ patient-derived induced pluripotent stem cells (iPSCs), as a model of the neurodevelopmental aspect of disease pathogenesis. It was found that the de-toxifying ability of GSH is impaired in SZ cerebral cells, offering a cogent target for further investigation in this novel approach to assessing the mechanisms of mental ill-health, in the brain.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
Aldred Dr,
Upthegrove Prof,
Wood Prof,
Licence: All rights reserved
College/Faculty: Colleges (2008 onwards) > College of Life & Environmental Sciences
School or Department: School of Sport, Exercise and Rehabilitation Sciences
Funders: Medical Research Council
Subjects: B Philosophy. Psychology. Religion > BF Psychology
Q Science > Q Science (General)
Q Science > QP Physiology
R Medicine > RB Pathology
R Medicine > RZ Other systems of medicine


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