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This dissertation, Modulating Effects of Chinese Green Tea on Hippocampal Neurons Against Glutamate Neurotoxicity and Hippocampal Dependent Memory During Aging in Mice by Yu, Fu, 傅玉, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of the thesis entitled Modulating Effects of Chinese Green Tea on Hippocampal Neurons Against Glutamate Neurotoxicity and Hippocampal Dependent Memory During Aging Submitted by Yu Fu for the degree of Master of Philosophy at The University of Hong Kong In October 2005 Oxidative stress is involved in and facilitates the pathogenesis of aging and neurodegenerative disorders. Excessive glutamate in the brain leads to oxidative stress and cell death. The glutamate induced oxidative can be utilized to investigate the cellular response to progressive oxidative stress during neurodegeneration. Previous studies have established that green tea is neuroprotective to other models of neurodegenerative disorders, but the effect and mechanism of green tea in glutamate neurotoxicity is still unclear. The objectives of the present study were (1) to determine the major components of Chinese green tea and investigate their effects and possible underling mechanisms on glutamate induced oxidative stress in mouse hippocampal neuronal cells, and (2) to evaluate the effect of chronic tea drinking on hippocampal dependent memory ability during aging process and correlate the findings in cell model with those in behavioral experiments. It was found that both of the two major Chinese green tea components, (-)-epigallocatechin-3-gallate (EGCG) and caffeine, protect hippocampal neuronal cells from glutamate induced oxidative stress, but through different mechanisms. EGCG was found to protect cells mainly through its antioxidative property, while caffeine protected cells through blockade of adenosine A receptors and induction of iiheme oxygenase-1 (HO-1) through a cAMP dependent pathway. In animal model, chronic tea drinking was found to effectively lower oxidative stress in hippocampus and induce expression of HO-1 in young adult (6 months old), mature adult (12 months old) and middle aged (18 months old) mice. Significant decline in hippocampal dependent cognitive ability was only found in 18 months old mice and such a decline was reversed by either fresh tea or tea powder drinking. The tea powder solution contains equivalent tea polyphenols and caffeine as fresh tea. Furthermore, better long-term memory retention ability was found in all age groups of tea drinking mice when compared with age-matched normal control. Taken together, the present studies established the mechanisms of the neuroprotective effects of major Chinese green tea components against glutamate induced oxidative stress and such effects were testified in animal model. It is suggested that tea drinking could serve as an effective way to counteract the decline of cognitive ability during aging. (355 words) iii DOI: 10.5353/th_b3201789 Subjects: Hippocampus (Brain)NeuronsGlutamic acidNeurotoxicologyOxidative stressGreen tea - Physiological effects

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