The influence of chronic cerebral hypoperfusion on cognitive function and amyloid β metabolism in APP overexpressing mice.
The influence of chronic cerebral hypoperfusion on cognitive function and amyloid β metabolism in APP overexpressing mice.
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DOI：
10.1371/journal.pone.0016567
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发表时间：
2011-01-27
期刊：
影响因子：
3.7
通讯作者：
Takahashi R
中科院分区：
文献类型：
--
作者：
Yamada M;Ihara M;Okamoto Y;Maki T;Washida K;Kitamura A;Hase Y;Ito H;Takao K;Miyakawa T;Kalaria RN;Tomimoto H;Takahashi R
由脑血管功能不全引起的认知障碍被称为血管性认知障碍，并且通常被认为与由神经退行性过程引起的阿尔茨海默病不同。然而，很明显，这种简单的二分法可能需要修改，在阿尔茨海默病和血管性认知障碍之间的几个共同特征的明显发生。然而，它仍然在很大程度上是未知的负担血管和阿尔茨海默型神经病理学是独立的或相互依赖的。因此，我们研究了慢性脑灌注不足是否影响淀粉样前体蛋白（APP）过表达转基因小鼠的认知能力或淀粉样β蛋白沉积。使用微弹簧圈或假手术对过度表达携带Swedish和印第安纳州突变的人APP的突变形式（APPSw/Ind-Tg小鼠）或其野生型同窝小鼠进行慢性脑灌注不足伴双侧颈总动脉狭窄（BCAS）。采用2×2析因实验设计，在8月龄时对4组大鼠的巴恩斯迷宫测试成绩和组织病理学结果进行分析。与其他三组小鼠相比，BCAS操作的APPSw/Ind-Tg小鼠显示出显著受损的学习能力。双向重复测量方差分析显示，APP基因型和BCAS操作之间的协同作用，在诱导学习障碍。认知能力与神经元密度显著相关。与假手术小鼠相比，BCAS显著降低了APPSw/Ind-Tg小鼠海马中Nissl染色神经元和银染核心斑块的密度，但增加了细胞外富集可溶性脑组分中过滤陷阱淀粉样蛋白β的量。结果表明，慢性脑灌注不足和APPSw/Ind过表达之间的相互作用通过增强神经元丢失和改变淀粉样β代谢在小鼠认知能力下降。
Cognitive impairment resulting from cerebrovascular insufficiency has been termed vascular cognitive impairment, and is generally accepted to be distinct from Alzheimer's disease resulting from a neurodegenerative process. However, it is clear that this simple dichotomy may need revision in light of the apparent occurrence of several shared features between Alzheimer's disease and vascular cognitive impairment. Nevertheless, it still remains largely unknown whether the burden of vascular- and Alzheimer-type neuropathology are independent or interdependent. Therefore, we investigated whether chronic cerebral hypoperfusion influences cognitive ability or amyloid β deposition in amyloid precursor protein (APP) overexpressing transgenic mice. Two months old mice overexpressing a mutant form of the human APP bearing both the Swedish and Indiana mutations (APPSw/Ind-Tg mice), or their wild-type littermates, were subjected to chronic cerebral hypoperfusion with bilateral common carotid artery stenosis (BCAS) using microcoils or sham operation. Barnes maze test performance and histopathological findings were analyzed at eight months old by 2×2 factorial experimental designs with four groups. BCAS-operated APPSw/Ind-Tg mice showed significantly impaired learning ability compared to the other three groups of mice. Two-way repeated measures analysis of variance showed a synergistic interaction between the APP genotype and BCAS operation in inducing learning impairment. The cognitive performances were significantly correlated with the neuronal densities. BCAS significantly reduced the density of Nissl-stained neurons and silver-stained cored plaques in the hippocampus of APPSw/Ind-Tg mice but increased the amount of filter-trap amyloid β in the extracellular-enriched soluble brain fraction, compared to those from sham operated mice. The results suggest interaction between chronic cerebral hypoperfusion and APPSw/Ind overexpression in cognitive decline in mice through enhanced neuronal loss and altered amyloid β metabolism.
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痴呆症的流行病学病理：医学研究委员会认知功能和衰老研究中死亡的可归因风险。
影响因子：
15.8
作者：
Matthews FE;Brayne C;Lowe J;McKeith I;Wharton SB;Ince P
通讯作者：
Ince P
影响因子：
2.9
作者：
Kitaguchi, Hiroshi;Tomimoto, Hidekazu;Takahashi, Ryosuke
通讯作者：
Takahashi, Ryosuke
DOI：
10.1037/h0077579
发表时间：
1979-01-01
期刊：
JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
BARNES, CA
通讯作者：
BARNES, CA
影响因子：
82.9
作者：
Shankar, Ganesh M.;Li, Shaomin;Selkoe, Dennis J.
通讯作者：
Selkoe, Dennis J.
影响因子：
2.5
作者：
Kitaguchi, Hiroshi;Ihara, Masafumi;Tomimoto, Hidekazu
通讯作者：
Tomimoto, Hidekazu