Date of Award

7-23-2024

Publication Type

Thesis

Degree Name

M.Sc.

Department

Biological Sciences

Supervisor

Siyaram Pandey

Abstract

Alzheimer’s disease (AD) is the most prevalent form of dementia, currently affecting approximately 35.6 million individuals globally with numbers expected to rise significantly in the near future. AD is characterized by progressive memory loss, brain volume loss, amyloid-β plaque depositions, and neurofibrillary tau tangles. Several biochemical factors contribute to the onset and progression of AD, including increased oxidative stress and neuroinflammation, mitochondrial dysfunction, disrupted synapses, and issues with autophagy and astroglial activation. Existing therapies can alleviate AD symptoms and target individual pathways. However, they often come with adverse side effects that can be problematic with long-term use and ultimately do not prevent disease progression. Therefore, there is a growing interest in alternative treatments that are safe for prolonged use in managing neurodegenerative diseases like AD. Natural Health Products (NHPs) have a longstanding history of medicinal benefits in traditional systems such as Ayurveda, the Traditional Indian Medicine system. Previous research has shown that Ubisol-Q10 (Ub-Q10), a water-soluble formulation of the recognized antioxidant coenzyme Q10, and ashwagandha root extract (ASH) have neuroprotective benefits. However, the combined effects of these NHPs in a “tonic” formulation require further exploration in AD models, which is the primary aim of this study. Treatment with these NHPs, particularly in the tonic group, resulted in reduced levels of reactive oxygen species markers both in vitro and in vivo. In cell models, ASH treatment appeared to upregulate autophagy activation, and tonic-treated cells showed reduced markers of cellular senescence compared to control. In a double transgenic AD mouse model, microglia activation, indicating inflammation, was decreased in the tonic group, as well as amyloid-β plaque formation. Astroglia activation, neurotrophic factors, and a marker of a synaptic vesicle protein were upregulated with tonic treatment. Memory changes measured in a robust 5XFAD mouse model suggest a potential slowed decline of spatial memory in tonic-treated animals with similar behavioural patterns to wild-type. Ubisol-Q10 and ashwagandha are GRAS-approved nutraceuticals that can be taken long-term without serious side effects. As such, these NHPs may improve prognosis and quality of life for AD patients.

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