碩士 / 國防醫學院 / 生物及解剖學研究所 / 104 / Alzheimer’s disease (AD) is a progress neurodegenerative disorder that associated with the defects of cognition and memory. Recent studies showed that insulin resistant in the brain may play an important role in the etiopathogenesis of the sporadic AD (sAD). In this study, the SD rat with streptozotocin intracerebroventricular (STZ-icv) treatment was used to be a sAD animal model. The open field test (OFT) and radial arm maze (RAM) behavior test were carried out to evaluate the cognitive and memory deficits in STZ-icv rat. Moreover, the [18F]FDG and [18F]T807 coupled with animal positron emission tomography (animal-PET) were also used to evaluate the status of brain glucose metabolism and the expression of paired helical filament (PHF)-tau protein, respectively. Volumes of interest (VOIs) of brain regions were drawn on PET images and compared between control and STZ-icv rats. We also examined the neuroprotective effects of dextromethorphan (DM) and pregnenolone sulfate (PS) in STZ-icv rat. After the last PET scanning, all the rats were sacrificed for the phosphorylated tau and glucose transporter 3 (GLUT3) immunohistochemical (IHC) staining. The results of OFT and RAM tests showed cognitive and memory deficits in STZ-icv induced sAD rat. The PET images showed that [18F]FDG uptakes was decreased and [18F]-T807 uptake was increased in the rat brains after STZ-icv injection. The STZ-icv rats with DM or PS treatments showed significant uptake changes of [18F]FDG and [18F]T807 in rat brains. Previous studies have shown that DM can be improved caused by NMDA receptors adjusting the neurotoxicity hypoxia and neuronal damage. And pregnenolone sulfate is the most abundant and primitive steroid in the rat and human nerve tissue. Early studies have indicated pregnenolone sulfate has anti-inflammatory and inhibit oxidative stress in the central nervous system. In this study the results showed that both drugs have neuroprotective effects against the STZ-induced neurotoxicity. The results of this study may clarify the toxicity of STZ in the rat brains, and the model may provide a platform for in developing novel therapeutic druds for AD.
| Identifer | oai:union.ndltd.org:TW/104NDMC0589010 |
| Date | January 2016 |
| Creators | CHUANG, CHING-YU, 莊靖渝 |
| Contributors | MA, KUO-HSING, KANG, HSIAO-HSIEN, 馬國興, 康孝先 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 68 |
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