碩士 / 國立陽明大學 / 生物藥學研究所 / 102 / Alzheimer's disease (AD) was the most common dementia in the elderly. In addition to genetic inheritance, there were many non-genetic risk factors lead to AD. According to epidemiological statistics, diabetes and AD had a positive correlation between the occurrences. Neurofibrillary tangles and senile plaques were AD of the two major pathological signs. On the other hand, insulin played an important role in the nervous system; it maintained the survival of nerve cells and promoted memory and learning. The aim of this study was to identify db/db-diabetic mice brain related to AD. Furthermore, the animal model was used to evaluate the therapeutic potential of traditional Chinese medicines with activating blood circulation and removing blood stasis on AD. Leptin receptor-deficient db/db mice was a model of type 2 diabetes, its hippocampus displayed a series alterations. Tau phosphorylation was higher in db/db mice. We found that Akt, the insulin signaling protein, was age-dependently activated in db/db mice, but the phosphorylation of its downstream Gsk3β was not changed. These results demonstrated that the up-regulation of pTau in db/db was not caused by insulin resistant. Microglia in molecular layer was deramified age-dependently in db/db mice. Simultaneously, we used GFAP and S100B as the markers of astrocytes in different development stages. The expression of S100B was age-dependently increased in CA3, but the expression of GFAP was not changed with age in db/db mice. These results demonstrated that long-term diabetes was able to over activate astrocytes instead of inducing astrocytes proliferation (astrogliosis). In db/db mice, there was aberrant terminal dendritic development of doublecortin (DCX) immature neurons, but the exhibitions in Ki-67 (cell proliferating marker) and BrdU (cell mitotic marker) were not significantly different between non-diabetic and diabetic mice. These results suggested that diabetes affected neurogenesis during neuron maturation, but not during mitosis stage. Based on results above, diabetes accelerated aging in brain, caused pTau increased the formation of neurofibrillary tangles; hyper activation of glial cells, also mad neurogenesis deterioration. All the reasons led to the occurrence of AD. After db/db mice were fed with BHD and TGD for 4 weeks, the phosphorylation of Akt increased in diabetic mice, but the hyper-phosphorylation of tau still existed. We speculated that it might take longer duration, or higher dose to achieve the prospective effect. After db/db mice were fed with XZD for 4 weeks, the morphology of microglia turned to atrophy type, the astrocytes activation was inhibited, and neurogenesis was reduced. These results suggest that TGD and BHD could slightly improve brain insulin resistance; Alternatively, XZD was harmful to glia cell and neurogenesis in T2DM mice.
| Identifer | oai:union.ndltd.org:TW/102YM005603017 |
| Date | January 2014 |
| Creators | Yun-Li Lien, 連芸儷 |
| Contributors | Yong-Ji Shiao, 蕭永基 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 60 |
Page generated in 0.0201 seconds