Chronic cerebral hypoperfusion in a mouse model of Alzheimer's disease: An additional contributing factor of cognitive impairment
Chronic cerebral hypoperfusion in a mouse model of Alzheimer's disease: An additional contributing factor of cognitive impairment
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DOI：
10.1016/j.neulet.2010.11.071
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发表时间：
2011-02-04
影响因子：
2.5
通讯作者：
Joo, In Soo
中科院分区：
文献类型：
--
作者：
Lee, Jin Soo;Im, Doo Soon;Joo, In Soo
本研究的目的是评估慢性脑灌注不足是否会影响阿尔茨海默病小鼠模型的认知状态。使用雌性Tg 2576小鼠在右颈总动脉闭塞（rCCAO）后8周进行行为测试和组织学评价，已知rCCAO在非转基因小鼠中诱导一种无神经元坏死的血管性痴呆。正电子发射断层扫描（18）F-氟脱氧葡萄糖（FDG-PET）被用来评估非转基因小鼠的rCCAO手术的大脑代谢状态。从Morris水迷宫测试的逃避潜伏期rCCAO和假手术小鼠之间没有显着差异。然而，学习曲线受损的rCCAO操作的转基因小鼠，而它被保存在假手术的转基因或rCCAO操作的非转基因小鼠。组织学检查显示，在rCCAO手术的大脑中没有细胞死亡的证据，淀粉样蛋白沉积的程度在rCCAO和假手术小鼠中没有差异。通过FDG-PET，rCCAO手术小鼠的大脑在同侧顶叶皮质中显示代谢缺陷。总之，在阿尔茨海默病小鼠模型中，慢性脑灌注不足诱导了与典型阿尔茨海默病更相似的进一步认知下降。这种恶化可能与慢性脑灌注不足引起的代谢低下有关。(C)2010爱思唯尔爱尔兰有限公司版权所有。
The purpose of the present study was to evaluate whether chronic cerebral hypoperfusion would affect cognitive status in an Alzheimer mouse model. Behavioral tests and histological evaluations were performed using female Tg2576 mice eight weeks after right common carotid artery occlusion (rCCAO), which is known to induce a type of vascular dementia without neuronal necrosis in nontransgenic mice. Positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) was utilized to evaluate metabolic status in the rCCAO-operated brain of nontransgenic mice. Escape latency from the Morris water maze test was not significantly different between rCCAO- and sham-operated mice. However, the learning curve was impaired in rCCAO-operated transgenic mice while it was preserved in sham-operated transgenic or rCCAO-operated nontransgenic mice. Histological examination revealed no evidence of cell death in the rCCAO-operated brains, and the extent of amyloid deposition was not different in rCCAO- and sham-operated mice. The brain of rCCAO-operated mice showed metabolic deficits in the ipsilateral parietal cortex through FDG-PET. In conclusion, further cognitive decline which is more comparable to typical Alzheimer's disease was induced by chronic cerebral hypoperfusion in an Alzheimer mouse model. This aggravation might be associated with hypometabolism via chronic cerebral hypoperfusion. (C) 2010 Elsevier Ireland Ltd. All rights reserved.