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Analysis On The Expression Of Dynamin Isoforms In Transgenic Murine Model Of Alzheimer's Disease

Posted on:2013-01-12Degree:MasterType:Thesis
Country:ChinaCandidate:M ZhaoFull Text:PDF
GTID:2214330371978128Subject:Biochemistry and Molecular Biology
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Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by confusion and impaired memory. Dynamin family is a GTPase and the essential role of dynamin in vesicle scission and synaptic function has been widely supported. In this study, we used different transgenic murine model of AD to detect the expression of dynamin to investigate the molecular mechanism of cognition changes that dynamin involved and identify whether dynamin could be used as a novel marker for assessing the effect of AD therapeutic drug.First, based on the optimized procedure of protein extraction of brain tissue, we detect the dynamin of brain tissue both in protein and mRNA levels, respectively. When compared to C57mice, data showed that mRNA levels of dynamin was significantly down-regulated in3-week and3-month age3xTg AD mice, with the toppest decline by83.7%. However, only dynaminl was significantly down-regulated in6-month age and8-month age age3xTg AD mice. These results showed that the expression level of dyanminl was inversely related to the development of AD and might participate in the early development of AD.Next, in this study the expression of dynamin was also investigated in the3xTg AD mice with anti-Aβ sera. A significant increase of dynaminl (-59.3%) in mRNA expression and (-72%) in protein expression was detected in3xTg AD mice treated with anti-AP sera when compared to the untreated group. Furthermore, after active immunity, a significant increase both in the mRNA levels (~176.6%) and protein levels (-89.8%). These results showed that the up-regulation of dynaminl was well correlated with effects of the immune therapy.Taken collectively, our findings suggested that the down-regulation of dynaminl was an early event in the progression of AD. In addition, results in this study showed the significance of dynaminl as a candidate gene for further study on the pathogenesis of AD. Based on these data of behavioral improvement, these results identified that dynaminl as an attractive and promising marker for assessing the effect of AD immunotherapy drug.
Keywords/Search Tags:Alzheimer's disease, transgenic murine model of AD, dynamin, expression level, immunotherapy
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