Differential central pathology and cognitive impairment in pre-diabetic and diabetic mice
Differential central pathology and cognitive impairment in pre-diabetic and diabetic mice
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DOI：
10.1016/j.psyneuen.2013.05.010
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发表时间：
2013-11-01
影响因子：
3.7
通讯作者：
Garcia-Alloza, Monica
中科院分区：
文献类型：
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作者：
Jose Ramos-Rodriguez, Juan;Ortiz, Oscar;Garcia-Alloza, Monica
虽然年龄仍然是阿尔茨海默病（AD）和血管性痴呆（VD）的主要危险因素，但2型糖尿病（T2 D）已成为痴呆的相关危险因素。然而，这种关联的最终潜在机制仍不清楚。在本研究中，我们分析了db/db小鼠（瘦素受体KO小鼠）长期胰岛素抵抗和T2 D的中枢神经系统（CNS）形态和功能后果。我们还包括用高脂肪饮食（HFD）喂养的C57 B16小鼠和第三组C57 B16链脲佐菌素（STZ）处理的小鼠。Db/db小鼠表现出模拟AD和VD的病理学特征，包括年龄依赖性认知恶化、脑萎缩、自发性脑萎缩和tau蛋白磷酸化增加，优先影响皮质。在STZ诱导的糖尿病小鼠中观察到类似的情况。此外，代谢参数，如体重，葡萄糖和胰岛素水平是db/db小鼠中许多这些变化的良好预测因子。此外，在C57 B16小鼠中HFD诱导的高胰岛素血症中，我们仅观察到轻度CNS改变，表明中枢神经系统功能障碍与明确的T2 D相关。总之，我们的研究结果表明，T2 D可能会促进痴呆症中观察到的许多病理和行为改变，支持致力于控制葡萄糖稳态的干预措施可以改善痴呆症的进展和预后。(C)2013爱思唯尔有限公司保留所有权利。
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.