长链非编码RNA AK036689在阿尔茨海默病早期海马突触环路功能障碍中的作用

Alzheimer's disease is a neurodegenerative disease characterized by the deficits of learning and memory and seriously damages mental and physical health of elderly people. However, the underlying mechanisms are still missing. Recently, the role of long non-coding RNAs (lncRNA) and other epigenetics factors in the pathogenesis of sporadic AD has been gained extensively attention. By using lncRNA array, we found that lncRNA AK036689 is abnormally downregulated in the hippocampus of APP/PS1 mice, a well-known AD mice model. Moreover, the expression of AK036689 is similar to the hippocampus of AD patients. Injection of lentivirus that packaged with effective shRNA to AK036689 to the dentate gyrus of hippocampus in the mice induces the Alzheimer’s like dysfunction of pattern separation, suggesting its potential role in the deficits of neural circuits for learning and memory in the early stage of AD. But the mechanisms remains unknown. Here, we will explore the detailed roles and mechanisms of AK036689 in the dysfunction of hippocampal neural circuits of AD and evaluate the significance of lncRNA manipulation in the early prevention of AD by using bioinformatics, molecular biological, electrophysiological, molecular imaging and behavioral approach.

阿尔茨海默病（AD）是以学习记忆障碍为特征的神经退行性疾病，严重危害老年人群身心健康，但机制不明。近年来，长链非编码RNA（lncRNA）等表观遗传因素在散发型AD发病中的作用得到广泛关注。利用lncRNA芯片，我们发现lncRNA AK036689在AD模型小鼠APP/PS1的海马表达水平明显降低且与AD患者海马内变化趋势相同。在2月龄的APP/PS1小鼠（无病变）海马DG区注射特异性针对AK036689的shRNA病毒导致小鼠出现AD早期的模式分别功能障碍，提示其可能参与了AD早期海马突触环路障碍，但作用机理不清。本项目拟综合利用生物信息学、分子生物学、电生理、分子成像及行为学检测等手段，明确AK036689在AD的海马神经环路障碍中的作用及其机制并探索AK036689在AD脑内下降的机理，同时评估特异性调控AK036689在AD早期防治中的意义，为AD早期防治提供新的分子靶标。

阿尔茨海默病（AD）是以学习记忆障碍为特征的神经退行性疾病，严重危害老年人群身心健康，但机制不明。近年来，长链非编码RNA（lncRNA）等表观遗传因素在散发型AD发病中的作用得到广泛关注。利用lncRNA芯片，我们发现lncRNA AK036689在AD模型小鼠APP/PS1的海马表达水平明显降低且与AD患者海马内变化趋势相同。在2月龄的APP/PS1小鼠（无病变）海马DG区注射特异性针对AK036689的shRNA病毒导致小鼠出现AD早期的模式分别功能障碍，提示其可能参与了AD早期海马突触环路障碍，但作用机理不清。本项目拟综合利用生物信息学、分子生物学、电生理、分子成像及行为学检测等手段，明确AK036689在AD的海马神经环路障碍中的作用及其机制并探索AK036689在AD脑内下降的机理，同时评估特异性调控AK036689在AD早期防治中的意义，为AD早期防治提供新的分子靶标。