期刊
PSYCHONEUROENDOCRINOLOGY
卷 38, 期 11, 页码 2462-2475出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.psyneuen.2013.05.010
关键词
Alzheimer's disease; Vascular dementia; Type 2 diabetes; Spontaneous hemorrhage; Brain atrophy; Tau phosphorylation
资金
- ISCIII Ministerio de Economia y Competitividad, Spain [RYC-2008-02333]
- Junta de Andalucia, Proyectos de Investigacion de Excelencia [P11-CTS-7847]
- Instituto de Salud Carlos III
- FEDER (European Union)
- Fondo Europeo de Desarrollo Regional Una nnanera de hacer Europa [PI12/00675]
- ISCIII-Subdireccion General de Evaluacion y Fomento de la Investigacion, Spain [PS09/00671]
- Europe-FP7 Marie Curie Grant [IRG-247835]
- [RYC-2011-08101]
Although age remains the main risk factor to suffer Alzheimer's disease (AD) and vascular dementia (VD), type 2 diabetes (T2D) has turned up as a relevant risk factor for dementia. However, the ultimate underlying mechanisms for this association remain unclear. In the present study we analyzed central nervous system (CNS) morphological and functional consequences of long-term insulin resistance and T2D in db/db mice (leptin receptor KO mice). We also included C57Bl6 mice fed with high fat diet (HFD) and a third group of C57Bl6 streptozotocin (STZ) treated mice. Db/db mice exhibited pathological characteristics that mimic both AD and VD, including age dependent cognitive deterioration, brain atrophy, increased spontaneous hemorrhages and tau phosphorylation, affecting the cortex preferentially. A similar profile was observed in STZ-induced diabetic mice. Moreover metabolic parameters, such as body weight, glucose and insulin levels are good predictors of many of these alterations in db/db mice. In addition, in HFD-induced hyperinsulinemia in C57Bl6 mice, we only observed mild CNS alterations, suggesting that central nervous system dysfunction is associated with well established T2D. Altogether our results suggest that T2D may promote many of the pathological and behavioral alterations observed in dementia, supporting that interventions devoted to control glucose homeostasis could improve dementia progress and prognosis. (C) 2013 Elsevier Ltd. All rights reserved.
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