Similar pattern of peripheral neuropathy in mouse models of type 1 diabetes and Alzheimer's disease.
Similar pattern of peripheral neuropathy in mouse models of type 1 diabetes and Alzheimer's disease.
复制标题
1型糖尿病和阿尔茨海默氏病小鼠模型中外周神经病的类似模式。
DOI：
10.1016/j.neuroscience.2011.11.032
复制
发表时间：
2012-01-27
期刊：
影响因子：
3.3
通讯作者：
Masliah, E.
中科院分区：
文献类型：
--
作者：
Jolivalt, C. G.;Calcutt, N. A.;Masliah, E.
关键词：
人们越来越认识到糖尿病会对中枢神经系统产生影响，并且糖尿病是阿尔茨海默病 (AD) 的危险因素。 AD 和糖尿病之间的联系表明，胰岛素信号传导受损是导致大脑缺陷的常见机制。然而，糖尿病的主要特征是外周神经病变，而不是中枢神经病变，尽管 AD 和糖尿病有共同的中枢机制，但人们对 AD 对 PNS 的影响知之甚少。在这项研究中，我们比较了周围神经病变的指标，并研究了胰岛素缺乏小鼠和 APP 过表达转基因小鼠的坐骨神经中的胰岛素信号传导。胰岛素缺乏和 APP 转基因小鼠表现出相似的周围神经病变模式，包括运动神经传导速度降低、热痛觉减退和触觉敏感性丧失。尽管两种模型的血糖和血浆胰岛素水平显着不同，但胰岛素受体和 GSK3β 的磷酸化在胰岛素缺乏和 APP 转基因小鼠中受到类似的影响，并且神经显示 Aβ 免疫反应蛋白的积累。尽管糖尿病和AD有不同的主要病因，但这两种疾病在大脑和PNS方面都有许多异常。我们的数据指出了两种神经退行性疾病中胰岛素信号通路的常见缺陷，并支持 AD 可能导致高级中枢神经系统以外疾病的观点。
There is an increasing awareness that diabetes has an impact on the CNS and that diabetes is a risk factor for Alzheimer’s disease (AD). Links between AD and diabetes point to impaired insulin signaling as a common mechanism leading to defects in the brain. However, diabetes is predominantly characterized by peripheral, rather than central, neuropathy and despite the common central mechanisms linking AD and diabetes, little is known about the effect of AD on the PNS. In this study, we compared indices of peripheral neuropathy and investigated insulin signaling in the sciatic nerve of insulin-deficient mice and APP overexpressing transgenic mice. Insulin-deficient and APP transgenic mice displayed similar patterns of peripheral neuropathy with decreased motor nerve conduction velocity, thermal hypoalgesia and loss of tactile sensitivity. Phosphorylation of the insulin receptor and GSK3β were similarly affected in insulin-deficient and APP transgenic mice despite significantly different blood glucose and plasma insulin levels and nerve of both models showed accumulation of Aβ-immunoreactive protein. Although diabetes and AD have different primary etiologies, both diseases share many abnormalities in both the brain and the PNS. Our data point to common deficits in the insulin-signaling pathway in both neurodegenerative diseases and support the idea that AD may cause disorders outside the higher CNS.
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影响因子：
7.4
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