Insulin deficiency exacerbates cerebral amyloidosis and behavioral deficits in an Alzheimer transgenic mouse model.
Insulin deficiency exacerbates cerebral amyloidosis and behavioral deficits in an Alzheimer transgenic mouse model.
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DOI：
10.1186/1750-1326-5-46
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发表时间：
2010-11-02
影响因子：
15.1
通讯作者：
Wang ZY
中科院分区：
文献类型：
--
作者：
Wang X;Zheng W;Xie JW;Wang T;Wang SL;Teng WP;Wang ZY
虽然越来越多的证据表明脑胰岛素功能障碍是阿尔茨海默病（AD）的危险因素，但胰岛素缺乏可能影响AD发展的潜在机制仍不清楚。利用链脲佐菌素（STZ）诱导的胰岛素缺乏型糖尿病AD转基因小鼠模型，我们评估了胰岛素缺乏对AD样行为和神经病理学的影响。结果表明，STZ可使APP/PS1小鼠血糖升高，血清胰岛素水平降低，胰岛素受体磷酸化水平进一步降低，糖原合成酶激酶3α/β和c-Jun氨基末端激酶活性升高。我们进一步表明，STZ处理促进了淀粉样蛋白-β（Aβ）前体蛋白的加工，导致转基因小鼠中Aβ生成增加、神经炎斑形成和空间记忆缺陷。我们目前的数据表明，在AD的发病机制中，胰岛素缺乏型糖尿病和脑淀粉样变性之间存在密切联系。
Although increasing evidence has indicated that brain insulin dysfunction is a risk factor for Alzheimer disease (AD), the underlying mechanisms by which insulin deficiency may impact the development of AD are still obscure. Using a streptozotocin (STZ)-induced insulin deficient diabetic AD transgenic mouse model, we evaluated the effect of insulin deficiency on AD-like behavior and neuropathology. Our data showed that administration of STZ increased the level of blood glucose and reduced the level of serum insulin, and further decreased the phosphorylation levels of insulin receptors, and increased the activities of glycogen synthase kinase-3α/β and c-Jun N-terminal kinase in the APP/PS1 mouse brain. We further showed that STZ treatment promoted the processing of amyloid-β (Aβ) precursor protein resulting in increased Aβ generation, neuritic plaque formation, and spatial memory deficits in transgenic mice. Our present data indicate that there is a close link between insulin deficient diabetes and cerebral amyloidosis in the pathogenesis of AD.
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