三转基因老年痴呆模型小鼠的生物节律特征及机制研究

项目名称： 三转基因老年痴呆模型小鼠的生物节律特征及机制研究

项目编号： No.31300968

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 武美娜

作者单位： 山西医科大学

项目金额： 22万元

中文摘要： 睡眠周期与生物节律的改变是阿尔茨海默病（Alzheimer's disease, AD）最常见的临床症状之一。在哺乳类动物，睡眠周期与机体各种生理功能的生物节律由下丘脑的视交叉上核（suprachiasmatic nucleus, SCN）调节，生物节律紊乱及其所导致的多种生理功能的紊乱会影响学习记忆功能，并进一步恶化AD症状。三转基因AD模型小鼠（triple-transgenic model, 3xTg-AD）是一种能够表现AD主要病理特征，模拟AD病程的最佳动物模型。目前已有少量关于3xTg-AD模型小鼠生物节律改变的行为学研究，但对AD病程中生物节律改变的具体特征和机制仍不明确。本研究将采用跑轮活动行为学测试、SCN脑片细胞外单单位放电记录和实时定量PCR技术进一步探讨该模型小鼠生物节律变化的特征和可能的机制，从而为预防和治疗AD病程中的生物节律紊乱，减缓AD进程提供新的策略。

中文关键词： 阿尔茨海默病；昼夜节律；视交叉上核；跑轮活动；

英文摘要： Alzheimer's disease (AD) is one of the most common form of dementia among the elderly, which is severely impaired the health and lifetime of old persons. In addition to progressive impairment of memory and cognitive performance, alteration of circadian rhythm and sleep pattern is one of the most common symptoms in Alzheimer patients. In mammals, sleep schedule and circadian variation of many phsiological functions are regulated by a circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus. AD patients tend to doze off during the day but wonder around the house at night. The increased daytime sleepiness worsens cognitive performance, while the fragmented nocturnal sleep further impairs memory consolidation during sleep and other symptoms in AD. Although the exact neuropathogenesis of AD remains unknown, neuritic plaques and neurofibrillary tangles are pathological hallmarks in the postmortem brain. The triple-transgenic (3xTg-AD) mouse, which is one of the best animal models of AD, expresses all three genes associated with familial AD and exhibits both amyloid plaques and neurofibrillary tangles in a comparable manner to that observed in AD patients. Recently, part of the behavioral abnormality in circadian rhythmicity of the 3xTg-AD mice was reported, but the whole characterization and the mechan

英文关键词： Alzheimer's disease；circadian rhythm；suprachiasmatic nucleus；wheel running activity；