Effect of aging and Alzheimer's disease-like pathology on brain monoamines in mice

被引:28
作者
Von Linstow, C. U. [1 ]
Severino, M. [1 ]
Metaxas, A. [1 ]
Waider, J. [2 ]
Babcock, A. A. [1 ]
Lesch, K. P. [2 ]
Gramsbergen, J. B. [1 ]
Finsen, B. [1 ]
机构
[1] Univ Southern Denmark, Inst Mol Med, Dept Neurobiol, JB Winslows Vej 25, DK-5000 Odense C, Denmark
[2] Univ Wurzburg, Sect Mol Psychiat, Ctr Mental Hlth, Lab Translat Neurosci, Fuechsleinstr 15, D-97080 Wurzburg, Germany
关键词
Amyloid precursor protein/presenilin 1; Neocortex; Brainstem; Serotonin; Dopamine; Noradrenaline; AGE-RELATED-CHANGES; BETA-AMYLOID LOAD; RAT-BRAIN; 5-HYDROXYINDOLEACETIC ACID; HOMOVANILLIC-ACID; CEREBRAL-CORTEX; BIOGENIC-AMINES; DTG APP/PS1; DOPAMINE; METABOLITES;
D O I
10.1016/j.neuint.2017.04.008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Aging is the greatest single risk factor of the neurodegenerative disorder Alzheimer's disease (AD). The monoaminergic system, including serotonin (5-HT), dopamine (DA) and noradrenaline (NA) modulates cognition, which is affected in AD. Changes in monoamine levels have been observed in AD, but these can both be age- and/or disease-related. We examined whether brain monoamine levels change as part of physiological aging and/or AD-like disease in APP(SWE)/PS1(Delta E9) (APP/PS1) transgenic mice. The neocortex, hippocampus, striatum, brainstem and cerebellum of 6-, 12-, 18- and 24-month-old B6C3 wild-type (WT) mice and of 18-month old APP/PS1 and WT mice were analysed for 5-HT, DA and NA contents by high pressure liquid chromatography (HPLC), along with neocortex from 14-month-old APP/PS1 and WT mice. While, we observed no aging effect in WT mice, we detected region-specific changes in the levels of all monoamines in 18-month-old transgenic compared with WT mice. This included reductions in 5-HT (-30%), DA (-47%) and NA (-32%) levels in the neocortex and increases of 5-HT in the brainstem (+18%). No changes were observed in any of the monoamines in the neocortex from 14-month-old APP/ PS1 mice. In combination, these findings indicate that aging alone is not sufficient to affect brain monoamine levels, unlike the APPswE/PS1,6,E9 genotype. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码:238 / 245
页数:8
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