碩士 / 國立陽明大學 / 生物醫學影像暨放射科學系 / 105 / Alzheimer’s disease (AD) is a progressively neurodegenerative disease, resulting in gradual cognitive deficits and memory impairment. There are some critical features in the brain of AD patients, such as neuronal loss, extracellular β-amyloid (Aβ) deposition, intracellular neurofibrillary tangles, as well as severe inflammation. Intracellular Aβ accumulation would induce oxidative stress and mitochondrial dysfunction, which have been reported were the important mechanisms for neuronal degeneration. CDGSH Iron Sulfur Domain 2 (Cisd2) is the important gene for maintaining mitochondrial integrity and functions. Cisd2 deficiency leads to mitochondrial breakdown and loss-of-function, and subsequently other premature aging phenotypes in mice. On the contrary, a persistent level of Cisd2 in whole life prolongs health-span and lifespan, due to effectively ameliorate the aged defects on muscles, neurons and other organs. However, the effects of Cisd2 levels on the brain functions, even the pathologies of AD, have not been demonstrated. Our previous data have shown that Cisd2 expression decreased with age in mouse brain. We hypothesized that the changes of Cisd2 levels will be a critical factor for the functionalities of brain during aging or neurodegeneration.
Super-resolution track density image (TDI) provides higher spatial resolution and enhanced the contrast between grey matter and white matter contoured hippocampus precisely. In this study, we combined the diffusion MRI technology and histological analyses to examine the effects of Cisd2 on mouse brain. Our results showed that the volume ratio of hippocampus was obviously decreased in the Cisd2 knockout brains, caused by neuronal loss. Cisd2 overexpression could effectively ameliorate the brain pathologies, including the changes of brain volume, neuronal loss and neuroinflammation. By integrating multiple techniques, including MRI and histology, we proved the maintenance of Cisd2 expression is a crucial point on brain functionalities.
| Identifer | oai:union.ndltd.org:TW/105YM005605013 |
| Date | January 2017 |
| Creators | Chung-Guang Chen, 陳重光 |
| Contributors | Ching-Po Lin, Chia-Hao Su, Ting-Fen Tsai, 林慶波, 蘇家豪, 蔡亭芬 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 61 |
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