Activation of mammalian target of rapamycin signaling in spatial learning
Activation of mammalian target of rapamycin signaling in spatial learning
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DOI：
10.1016/j.neures.2010.06.008
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发表时间：
2010-10-01
影响因子：
2.9
通讯作者：
Takei, Nobuyuki
中科院分区：
文献类型：
--
作者：
Qi, Sihua;Mizuno, Makoto;Takei, Nobuyuki
新型蛋白质合成是各种学习范式的基本要素。虽然药理学和遗传学策略已经表明了翻译激活在学习中的重要性，但在大脑中激活的特定信号通路仍然不清楚。在这里，我们表明，哺乳动物雷帕霉素靶蛋白（mTOR），一个关键的丝氨酸/苏氨酸蛋白激酶的翻译控制，激活学习大鼠的海马中所揭示的体外激酶测定，蛋白质印迹和免疫组织化学。mTOR的底物，真核起始因子4 E结合蛋白（4 EBP）和p70 S6激酶（p70 S6 K）被磷酸化，总蛋白质合成增强，在学习海马。此外，通过将雷帕霉素（一种mTOR的特异性抑制剂）长期输注到心室中来抑制mTOR，从而延迟了空间学习的建立。因此，mTOR信号在学习过程中被激活，增强翻译，并在空间学习中起着至关重要的作用。(C)2010年爱思唯尔爱尔兰有限公司和日本神经科学学会。All rights reserved.
Novel protein synthesis is an essential element of various learning paradigms. Although pharmacological and genetic strategies have indicated the importance of translational activation in learning, the specific signaling pathways that are activated in the brain remain unclear. Here, we show that mammalian target of rapamycin (mTOR), a key serine/threonine protein kinase in translational control, is activated in hippocampus of the learning rat as revealed by in vitro kinase assay, Western blotting and immunohistochemistry. The substrates of mTOR, eukaryotic initiation factor 4E-binding protein (4EBP) and p70S6 kinase (p70S6K) are phosphorylated, and total protein synthesis is enhanced, in the learning hippocampus. Furthermore, the inhibition of mTOR by chronic infusion of rapamycin, a specific inhibitor of mTOR, into the ventricle retards the establishment of spatial learning. Thus, mTOR signaling is activated during learning, enhances translation, and plays a crucial role in the spatial learning. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.