Department of Molecular Neurobiology, Brain Research Institute, Niigata University, 1, Asahimachi, Niigata 951-8585, Japan.
Neurosci Res. 2010 Oct;68(2):88-93. doi: 10.1016/j.neures.2010.06.008. Epub 2010 Jun 25.
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.
新蛋白质的合成是各种学习模式的一个基本要素。虽然药理学和遗传学策略表明翻译激活在学习中的重要性，但在大脑中被激活的特定信号通路仍不清楚。在这里，我们展示了雷帕霉素靶蛋白（mTOR），一种翻译控制中的关键丝氨酸/苏氨酸蛋白激酶，在学习大鼠的海马体中被激活，这是通过体外激酶测定、Western 印迹和免疫组织化学显示的。mTOR 的底物，真核起始因子 4E 结合蛋白（4EBP）和 p70S6 激酶（p70S6K）被磷酸化，并且在学习的海马体中总蛋白质合成增强。此外，雷帕霉素（mTOR 的特异性抑制剂）通过脑室的慢性输注抑制 mTOR，会延迟空间学习的建立。因此，mTOR 信号在学习过程中被激活，增强了翻译，并在空间学习中发挥了关键作用。
