Endothelial nitric oxide deficiency promotes Alzheimer's disease pathology

被引：143

作者：

Austin, Susan A. ^{[1
]}

Santhanam, Anantha V. ^{[1
]}

Hinton, David J. ^{[2
]}

Choi, Doo-Sup ^{[2
]}

Katusic, Zvonimir S. ^{[1
,2
]}

机构：

[1] Mayo Clin, Dept Anesthesiol, Rochester, MN 55905 USA

[2] Mayo Clin, Rochester, MN 55905 USA

来源：

JOURNAL OF NEUROCHEMISTRY | 2013年 / 127卷 / 05期

基金：

美国国家卫生研究院;

关键词：

Alzheimer's disease; amyloid precursor protein; endothelium; memory; microglia; nitric oxide; AMYLOID BETA-PROTEIN; MAZE PERFORMANCE; EXPRESSION; MOUSE; BRAIN; DYSFUNCTION; INHIBITION; HIPPOCAMPUS; NEURONS; DAMAGE;

D O I：

10.1111/jnc.12334

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Aging and the presence of cerebrovascular disease are associated with increased incidence of Alzheimer's disease. 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) (14-15month) endothelial nitric oxide synthase deficient (eNOS(-/-)) mice. APP, -site APP cleaving enzyme (BACE) 1, and amyloid beta (A) levels were significantly higher in the brains of LMA eNOS(-/-) mice as compared with LMA wild-type controls. APP and A(1-40) were increased in hippocampal tissue of eNOS(-/-) mice as compared with wild-type mice. LMA eNOS(-/-) mice displayed an increased inflammatory phenotype as compared with LMA wild-type mice. Importantly, LMA eNOS(-/-) mice performed worse in a radial arm maze test of spatial learning and memory as compared with LMA wild-type mice. These data suggest that chronic loss of endothelial NO may be an important contributor to both A related pathology and cognitive decline.

引用

页码：691 / 700

页数：10

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