碩士 / 國立臺灣師範大學 / 人類發展與家庭學系 / 102 / High fat-diet (HFD) promotes obesity, increases the risk of insulin resistance and diabetes mellitus (DM). It also contributes to brain insulin resistance and the pathogenesis of Alzheimer’s disease (AD). Epidemiologically, patients with Type 2 DM have a two-to three-fold increased risk for AD. We previously confirmed caffeic acid improves glucose metabolism and alleviates insulin resistance in cell and animal models. In this study, we further investigate the alleviative effect of caffeic acid on AD pathogenesis and associated mechanisms in HFD (60% fat) induced hyperinsulinemic rats.
According to the results of Morris water maze, caffeic acid (30mg/ kg b.w./ day) significantly ameliorated memory and learning impairment in hyperinsulinemic rats. Caffeic acid enhanced superoxide dismutase (SOD) activity and the glutathione free radical scavenger activity in hyperinsulinemic rats. The results from western blotting shows that protein expressions of p-AKT/Protein kinase B (p-AKT/ PKB), p-glycogen synthase kinase3β (p-GSK3β) significantly increased, whereas, the expression of p-tau decreased in hippocampus of rats administered with caffeic acid compared with the hyperinsulinemic control group. Besides, the expression of amyloid precursor protein (APP) and β-site APP cleaving enzyme (BACE) were attenuated in the hippocampus of hyperinsulinemic rats treated with caffeic acid, therefore lowered the level of β-amyloid 1-42(Aβ 1-42). Experimentally, caffeic acid increased the expressions of brain-derived neurotrophic factor (BDNF) and synaptic protein in the cortex compared with the hyperinsulinemic control group. Compensatory effect of insulin degrading ezyme (IDE) in hyperinsulinemic rats was also reduced by the administration of caffeic acid.
Above observation suggests that caffeic acid may exhibit the neuroprotective effect via improves insulin/leptin signaling, decreases oxidative stress, attenuates the hyperphosphorylation of tau protein and amyloidgenic pathway, and upregulates the expression of neurotrophic factor, thus may prevent the pathogenesis of AD.
| Identifer | oai:union.ndltd.org:TW/102NTNU5261025 |
| Date | January 2014 |
| Creators | TEE QIN QIAO, 鄭勤巧 |
| Contributors | , 沈賜川, 吳瑞碧 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 134 |
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