期刊
NEUROSCIENCE LETTERS
卷 468, 期 3, 页码 243-247出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2009.11.005
关键词
Alzheimer disease; Noradrenaline; Locus ceruleus; Amyloid beta-protein; Tau; Tau phosphorylation; Testosterone
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [1700220004]
Locus ceruleus (LC) neurons are preferentially and initially affected in Alzheimer disease (AD); however, the impact of the loss of LC neurons on the pathological sequence of AD, including amyloid P-protein (A beta) deposition and neurofibrillary tangle formation, has not been elucidated. In this study, we chemically injured LC neurons of the brains of familial AD-related amyloid precursor protein (APP)-transgenic mice using the LC-noradrenergic neuron-selective neurotoxin, N-(2-chloroethyl)-N-ethyl-bromo-benzylamine (DSP4). The levels of noradrenaline significantly decreased in the cerebral cortices of DSP4-treated mice. The deposition of amyloid fibrils was biochemically observed in the APP-transgenic mouse brains; however, those levels were not significantly altered following DSP4 treatment. In contrast, the levels of accumulated hyperphosphorylated tau markedly increased in the cerebral cortices of DSP4-treated female but not male APP-transgenic mice. Our results suggest that innervation from LC neurons and testosterone secretion are potent and mutually independent suppressors of amyloid-related accumulation of hyperphosphorylated tau in the brain. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据