Gender effect on the accumulation of hyperphosphorylated tau in the brain of locus-ceruleus-injured APP-transgenic mouse.
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 beta-protein (Abeta) 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.
Oikawa
Naoto
N
Department of Alzheimer's Disease Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3, Gengo, Morioka, Obu 474-8522, Japan.
Ogino
Koichi
K
Masumoto
Takumi
T
Yamaguchi
Haruyasu
H
Yanagisawa
Katsuhiko
K
D000682:Amyloid / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001596:Benzylamines / Q000633:toxicity; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D008125:Locus Coeruleus / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism; D010766:Phosphorylation; D012737:Sex Factors; D013739:Testosterone / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D001596:Benzylamines; D016875:tau Proteins; D013739:Testosterone; C012102:DSP 4; D009638:Norepinephrine