Reduction of β-amyloid and γ-secretase by calorie restriction in female Tg2576 mice

NEUROBIOLOGY OF AGING

卷:36

Article

Schafer, Marissa J.^1,2,3  Alldred, Melissa J.^3,4  Lee, Sang Han⁵  Calhoun, Michael E.⁶  Petkova, Eva^7,8  Mathews, Paul M.^3,4  Ginsberg, Stephen D.^1,3,4,9 

[1] NYU, Langone Med Ctr, Cell & Mol Biol Program, New York, NY USA

[2] NYU, Dept Cell Biol, Langone Med Ctr, New York, NY 10016 USA

[3] Nathan S Kline Inst Psychiat Res, Ctr Dementia Res, Orangeburg, NY USA

[4] NYU, Dept Psychiat, Langone Med Ctr, New York, NY 10016 USA

[5] Nathan S Kline Inst Psychiat Res, Div Med Phys, Orangeburg, NY USA

[6] Sinq Syst, Silver Spring, MD USA

[7] NYU, Langone Med Ctr, Dept Child & Adolescent Psychiat, New York, NY USA

[8] Nathan S Kline Inst Psychiat Res, Div Child Psychiat, Orangeburg, NY USA

[9] New York Univ, Langone Med Ctr, Dept Neurosci & Physiol, New York, NY USA

关键词: Abeta;    Aging;    Alzheimer's disease;    Amyloid-beta precursor protein;    CA1 pyramidal neurons;    Calorie restriction;    Entorhinal cortex;    Hippocampus;    Microarray;    Mouse model;    qPCR;   

DOI  :  10.1016/j.neurobiolaging.2014.10.043

来源: Elsevier

【 摘 要 】

Research indicates that female risk of developing Alzheimer's disease (AD) is greater than that of males. Moderate reduction of calorie intake, known as calorie restriction (CR), reduces pathology in AD mouse models and is a potentially translatable prevention measure for individuals at-risk for AD, as well as an important tool for understanding how the brain endogenously attenuates age-related pathology. Whether sex influences the response to CR remains unknown. In this study, we assessed the effect of CR on beta-amyloid peptide (A beta) pathology and hippocampal CA1 neuron specific gene expression in the Tg2576 mouse model of cerebral amyloidosis. Relative to ad libitum (AL) feeding, CR feeding significantly reduced hippocampal A beta burden in 15-month-old female, but not age-matched male, Tg2576 mice. Sustained CR also significantly reduced expression of presenilin enhancer 2 (Psenen) and presenilin 1, components of the gamma-secretase complex, in Tg2576 females. These results indicate that long-term CR significantly reduces age-dependent female Tg2576 A beta pathology, which is likely to involve CR-mediated reductions in gamma-secretase-dependent amyloid precursor protein (APP) metabolism. (C) 2015 Elsevier Inc. All rights reserved.

【 授权许可】

Free