Date of Award

2009

Publication Type

Doctoral Thesis

Degree Name

Ph.D.

Department

Chemistry and Biochemistry

Keywords

Pure sciences, Biological sciences, Health and environmental sciences, Herbicides, Neuroprotection, Parkinson's disease

Supervisor

Dr. Siyaram Pandey

Rights

info:eu-repo/semantics/openAccess

Abstract

Parkinson's disease is caused due to the progressive loss of dopaminergic neurons in the brain. Less than 10% of cases have a strict familial etiology while more than 90% are sporadic. The mechanisms underlying neuronal cell death in Parkinson's disease have not been fully elucidated. Furthermore, there is currently no therapy available to prevent the progressive loss of neurons in Parkinson's disease. The objective of my research was to establish a sporadic model of Parkinson's disease and evaluate the neuroprotective effects of water soluble Coenzyme Q10. In this study, a model of paraquat-induced neurodegeneration in rats was used to evaluate the efficacy of water soluble Coenzyme Q10 as a neuroprotectant. The results revealed a loss of dopaminergic neurons in the substantia nigra pars compacta region of the brain in paraquat-injected rats. Increased levels of oxidative stress and activated astrocytes were also observed in rats treated with paraquat. Furthermore, the behavioural tests uncovered deficiencies in fine motor skills in these rats. In parallel, rats that received water soluble Coenzyme Q10 in their drinking water showed significant neuroprotection against paraquat toxicity including behavioral improvements, reduced loss of dopaminergic neurons and lowered levels of oxidative stress. Interestingly, this neuroprotection was accompanied by an increased numbers of activated astroglia in the midbrain. The ability of this formulation of Coenzyme Q10 as a therapeutic agent was also studied; preliminary results indicate that it offers neuroprotection. Pilot studies revealed that paraquat-induced dopaminergic loss increases with age. Altogether, this study confirmed the neurotoxicity of paraquat, especially wards dopaminergic neurons, and provided a rat model of Parkinson's disease suitable mechanistic and neuroprotective studies. This is the first preclinical evaluation of water soluble Coenzyme Q10 as a neuroprotectant for Parkinson's disease at clinically relevant doses.

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