灌注
医学
淀粉样前体蛋白
莫里斯水上航行任务
脑灌注不足
内科学
阿尔茨海默病
病理
内分泌学
神经科学
海马体
生物
疾病
作者
Hong Liu,Anfeng Xing,Xiaojuan Wang,Guozhen Liu,Li Liang
标识
DOI:10.1016/j.neurobiolaging.2011.05.027
摘要
Cerebrovascular hypoperfusion occurs prior to clinical symptoms of Alzheimer's disease (AD) and represents the most accurate indicator predicting whether an individual develops AD in a future time. In order to explore the contribution of cerebrovascular hypoperfusion to AD, cerebrovascular hypoperfusion induced by bilateral carotid occlusion surgery in adult rats was used to investigate its impacts on spatial memory, amyloid-β protein (Aβ) production and clearance in the brain. The progressive spatial memory deficits were observed through Morris water maze test of the rats with cerebrovascular hypoperfusion induced by occlusion surgery. The memory deficits were accompanied with the increase of brain Aβ associated with Aβ overproduction due to the increased expression of β-amyloid precursor protein (APP) and enhanced activities of amyloid precursor protein cleavage enzymes such as β- and γ-secretases. Western blot and immunohistochemisty studies further revealed that cerebrovascular hypoperfusion could induce abnormal expression of β-amyloid receptor proteins including the receptor for advanced glycation end products (RAGE) and low-density lipoprotein receptor-related protein-1 (LRP-1), and result in a shift of immunoreactivity between neurons and vasculatures. Taken together, our results suggested that chronic cerebrovascular hypoperfusion could cause memory impairment and Aβ accumulation in brain associated with increased generation and impaired clearance of Aβ. Cerebrovascular hypoperfusion plays an important role in the pathogenesis and development of AD.
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