Intracerebroventricular streptozotocin exacerbates Alzheimer-like changes of 3xTg-AD mice.
Intracerebroventricular streptozotocin exacerbates Alzheimer-like changes of 3xTg-AD mice.
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DOI：
10.1007/s12035-013-8539-y
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发表时间：
2014-02
影响因子：
5.1
通讯作者：
Gong, Cheng-Xin
中科院分区：
文献类型：
--
作者：
Chen, Yanxing;Liang, Zhihou;Tian, Zhu;Blanchard, Julie;Dai, Chun-ling;Chalbot, Sonia;Iqbal, Khalid;Liu, Fei;Gong, Cheng-Xin
关键词：
阿尔茨海默病(AD)涉及几种可能的分子机制，包括脑胰岛素信号转导和葡萄糖代谢受损。为了探讨代谢损伤在AD中的作用，我们将链脲佐菌素(STZ)注射到6月龄3xTg-AD小鼠的侧脑室，并在3-6周后研究了认知功能和AD样脑异常，如tau磷酸化和Aβ积聚。我们发现，STZ加重了3xTg-AD小鼠的短期和空间参考记忆的损害。我们还观察到，在链脲佐菌素治疗后，tau蛋白过度磷酸化和神经炎症增加，脑内胰岛素信号转导紊乱，突触可塑性和淀粉样蛋白β多肽减少。20个AD相关基因的表达发生了改变，包括参与淀粉样前体蛋白的加工、细胞骨架、葡萄糖代谢、胰岛素信号、突触功能、蛋白激酶和细胞凋亡的基因，提示STZ干扰了大脑中的多个代谢和细胞信号通路。这些发现为代谢损伤在AD中的作用提供了实验证据。
Alzheimer’s disease (AD) involves several possible molecular mechanisms, including impaired brain insulin signaling and glucose metabolism. To investigate the role of metabolic insults in AD, we injected streptozotocin (STZ), a diabetogenic compound if used in the periphery, into the lateral ventricle of the 6-month old 3xTg-AD mice and studied the cognitive function as well as AD-like brain abnormalities, such as tau phosphorylation and Aβ accumulation, 3–6 weeks later. We found that STZ exacerbated impairment of short-term and spatial reference memory in 3xTg-AD mice. We also observed an increase of tau hyperphosphorylation and neuroinflammation, a disturbance of brain insulin signaling, and a decrease of synaptic plasticity and amyloid β peptides in the brain after STZ treatment. The expression of 20 AD-related genes, including those involved in the processing of amyloid precursor protein, cytoskeleton, glucose metabolism, insulin signaling, synaptic function, protein kinases and apoptosis, was altered, suggesting that STZ disturbs multiple metabolic and cell signaling pathways in the brain. These findings provide experimental evidence of the role of metabolic insult in AD.
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影响因子：
3.9
作者：
Iqbal K;Wang X;Blanchard J;Liu F;Gong CX;Grundke-Iqbal I
通讯作者：
Grundke-Iqbal I
影响因子：
--
作者：
Craft, Suzanne;Baker, Laura D.;Montine, Thomas J.;Minoshima, Satoshi;Watson, G. Stennis;Claxton, Amy;Arbuckle, Matthew;Callaghan, Maureen;Tsai, Elaine;Plymate, Stephen R.;Green, Pattie S.;Leverenz, James;Cross, Donna;Gerton, Brooke
通讯作者：
Gerton, Brooke
影响因子：
8.2
作者：
Gimenez-Llort, L.;Blazquez, G.;Fernandez-Teruel, A.
通讯作者：
Fernandez-Teruel, A.
影响因子：
4.7
作者：
Gruenblatt, Edna;Salkovic-Petrisic, Melita;Hoyer, Siegfried
通讯作者：
Hoyer, Siegfried
影响因子：
7.7
作者：
Francis, George;Martinez, Jose;Toth, Cory
通讯作者：
Toth, Cory