Experimental induction of type 2 diabetes in aging-accelerated mice triggered Alzheimer-like pathology and memory deficits.
Experimental induction of type 2 diabetes in aging-accelerated mice triggered Alzheimer-like pathology and memory deficits.
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衰老加速小鼠中2型糖尿病的实验诱导触发了阿尔茨海默氏症样病理和记忆缺陷。
DOI：
10.3233/jad-131238
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Chauhan NB
中科院分区：
文献类型：
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作者：
Mehla J;Chauhan BC;Chauhan NB
阿尔茨海默病(AD)是一种年龄依赖性神经退行性疾病，约占晚发性非家族性/散发性AD的95%，占早发性家族性AD的约5%。一个代表散发性AD的相关模型的可用性对于测试候选疗法是至关重要的。新的证据表明糖尿病和阿尔茨海默病之间存在因果联系。糖尿病患者患阿尔茨海默病的可能性是普通人的1.5倍。加速衰老的小鼠模型(SAMP8)表现出AD早期的许多特征。鉴于糖尿病在AD易感性中所起的作用，以及SAMP8非转基因小鼠加速衰老模型的实用性，我们研究了高脂饮食诱导的SAMP8小鼠实验性2型糖尿病是否会引发脑的病理性衰老。结果显示，与非糖尿病SAMP8小鼠相比，糖尿病SAMP8小鼠大脑淀粉样蛋白β增加，tau-磷酸化糖原合成酶β表达失调，突触素免疫反应性降低，并表现出记忆障碍，表明阿尔茨海默病样变化。高脂饮食诱导的2型糖尿病SAMP8小鼠可能是AD的代谢模型。
Alzheimer’s disease (AD) is an age-dependent neurodegenerative disease constituting ~95% of late-onset non-familial/sporadic AD, and only ~5% accounting for early-onset familial AD. Availability of a pertinent model representing sporadic AD is essential for testing candidate therapies. Emerging evidence indicates a causal link between diabetes and AD. People with diabetes are >1.5-fold more likely to develop AD. Senescence-accelerated mouse model (SAMP8) of accelerated aging displays many features occurring early in AD. Given the role played by diabetes in the pre-disposition of AD, and the utility of SAMP8 non-transgenic mouse model of accelerated aging, we examined if high fat diet-induced experimental type 2 diabetes in SAMP8 mice will trigger pathological aging of the brain. Results showed that compared to non-diabetic SAMP8 mice, diabetic SAMP8 mice exhibited increased cerebral amyloid-β, dysregulated tau-phosphorylating glycogen synthase kinase 3β, reduced synaptophysin immunoreactivity, and displayed memory deficits, indicating Alzheimer-like changes. High fat diet-induced type 2 diabetic SAMP8 mice may represent the metabolic model of AD.