3xTgAD mice exhibit altered behavior and elevated Aβ after chronic mild social stress

NEUROBIOLOGY OF AGING

卷:33

Article

Rothman, Sarah M.¹  Herdener, Nathan¹  Camandola, Simonetta¹  Texel, Sarah J.¹  Mughal, Mohamed R.¹  Cong, Wei-Na²  Martin, Bronwen²  Mattson, Mark P.¹ 

[1] NIA, Lab Neurosci, Intramural Res Program, NIH, Baltimore, MD 21224 USA

[2] NIA, Lab Clin Invest, Intramural Res Program, NIH, Baltimore, MD 21224 USA

关键词: Alzheimer's disease;    Amyloid oligomers;    Psychosocial stress;    Corticosterone;    Hippocampus;    BDNF;   

DOI  :  10.1016/j.neurobiolaging.2011.07.005

来源: Elsevier

【 摘 要 】

Chronic stress may be a risk factor for developing Alzheimer's disease (AD), but most studies of the effects of stress in models of AD utilize acute adverse stressors of questionable clinical relevance. The goal of this work was to determine how chronic psychosocial stress affects behavioral and pathological outcomes in an animal model of AD, and to elucidate underlying mechanisms. A triple-transgenic mouse model of AD (3xTgAD mice) and nontransgenic control mice were used to test for an affect of chronic mild social stress on blood glucose, plasma glucocorticoids, plasma insulin, anxiety, and hippocampal amyloid beta-particle (A beta), phosphorylated tau (ptau), and brain-derived neurotrophic factor (BDNF) levels. Despite the fact that both control and 3xTgAD mice experienced rises in corticosterone during episodes of mild social stress, at the end of the 6-week stress period 3xTgAD mice displayed increased anxiety, elevated levels of A beta oligomers and intraneuronal A beta, and decreased brain-derived neurotrophic factor levels, whereas control mice did not. Findings suggest 3xTgAD mice are more vulnerable than control mice to chronic psychosocial stress, and that such chronic stress exacerbates A beta accumulation and impairs neurotrophic signaling. Published by Elsevier Inc.

【 授权许可】

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