Endothelial nitric oxide deficiency promotes Alzheimer's disease pathology.
Endothelial nitric oxide deficiency promotes Alzheimer's disease pathology.
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DOI：
10.1111/jnc.12334
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发表时间：
2013-12
影响因子：
4.7
通讯作者：
Katusic ZS
中科院分区：
文献类型：
--
作者：
Austin SA;Santhanam AV;Hinton DJ;Choi DS;Katusic ZS
老龄化和脑血管疾病的存在与阿尔茨海默病（AD）的发病率增加有关。衰老和脑血管疾病的共同特征是内皮一氧化氮（NO）减少。我们在中年晚期（LMA）（14-15个月）内皮型一氧化氮合酶缺陷（eNOS-/-）小鼠中研究了内皮源性NO的缺失对淀粉样前体蛋白（APP）相关表型的影响。与LMA野生型对照组相比，LMA eNOS−/−小鼠脑中的APP、β位点APP裂解酶（BACE）1和淀粉样β蛋白（Aβ）水平显著较高。与野生型小鼠相比，eNOS−/−小鼠海马组织中的APP和Aβ1-40增加。与LMA野生型小鼠相比，LMA eNOS−/−小鼠表现出增加的炎症表型。重要的是，与LMA野生型小鼠相比，LMA eNOS−/−小鼠在空间学习和记忆的径向臂迷宫测试中表现更差。这些数据表明，内皮NO的慢性丢失可能是Aβ相关病理和认知能力下降的重要因素。
Aging and the presence of cerebrovascular disease are associated with increased incidence of Alzheimer’s disease (AD). A common feature of aging and cerebrovascular disease is decreased endothelial nitric oxide (NO). We studied the effect of a loss of endothelium derived NO on amyloid precursor protein (APP) related phenotype in late middle aged (LMA) (14–15 month) endothelial nitric oxide synthase deficient (eNOS−/−) mice. APP, β-site APP cleaving enzyme (BACE) 1, and amyloid beta (Aβ) levels were significantly higher in the brains of LMA eNOS−/− mice as compared to LMA wild type controls. APP and Aβ1-40 were increased in hippocampal tissue of eNOS−/− mice as compared to wild type mice. LMA eNOS−/− mice displayed an increased inflammatory phenotype as compared to LMA wild type mice. Importantly, LMA eNOS−/− mice performed worse in a radial arm maze test of spatial learning and memory as compared to LMA wild type mice. These data suggest that chronic loss of endothelial NO may be an important contributor to both Aβ related pathology and cognitive decline.
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影响因子：
5.3
作者：
Hopper, Rachel A.;Garthwaite, John
通讯作者：
Garthwaite, John
影响因子：
3.3
作者：
Dere, E;Frisch, C;Huston, JP
通讯作者：
Huston, JP
DOI：
10.1073/pnas.1237107100
发表时间：
2003-05-27
影响因子：
11.1
作者：
Hoshi, M;Sato, M;Sato, K
通讯作者：
Sato, K
影响因子：
--
作者：
Arancio, O;LevRam, V;Hawkins, RD
通讯作者：
Hawkins, RD
影响因子：
25
作者：
Iadecola, C;Zhang, FY;Carlson, GA
通讯作者：
Carlson, GA