Med64关于胰岛素对幼鼠海马LTP表达的研究

Permissive role of insulin in the expression of long-term potentiation in the hippocampus of immature rats  

胰岛素对幼鼠海马长时程增强(LTP)表达的促进作用

Prof Yung WH/CUHK 香港中文大学

许多研究表明胰岛素信号传导失误导致学习和记忆障碍。不过，以前的研究不能确定胰岛素跟长时程增强 (LTP)的关联，虽然LTP为记忆形成的最佳细胞模型。在这里我们显示胰岛素预处理对成年大鼠海马长时程增强没有影响，但能促进还没成熟海马 LTP 表达。酪氨酸激酶抑制剂 AG-1024能取消胰岛素对幼鼠的影响， 所以胰岛素受体可能涉及在这个过程内。另一方面， 增加细胞外葡萄糖浓度不能促进LTP， 加入对胰岛素有作用的葡萄糖转运蛋白 4 抑制剂 （insulin-responsive glucose transporter-4 inhibitor）不会降低胰岛素的作用。这些结果表明胰岛素对 LTP 的促进不是一个间接的 胰岛素稳态/利用 机制。使用PD98059中断胰岛素介导 LTP ，得知胰岛素信号下游途径MAPK/ERK分子涉及在过程中。跟上述结果一致，高频刺激胰岛素处理海马增加磷酸化 Erk-2 水平。综上所述，这些研究结果表明胰岛素可能是未成熟的脑中，一个非常重要的物质以便 LTP出现 加强脑部的学习

原文地址：http://www.ncbi.nlm.nih.gov/pubmed/21346324

Many  studies indicate that impairment in insulin signaling leads to learning  and memory deficits. However, previous studies failed to establish a  clear role of insulin in long-term potentiation (LTP), the best cellular model of memory formation. Here we show that while insulin pretreatment  did not affect LTP magnitude in the adult rat hippocampus, it  facilitated LTP expression in the immature hippocampus. The tyrosine  kinase inhibitor AG-1024 abolished the effect of insulin in young rats,  suggesting the involvement of the insulin receptor. On the other hand,  increasing extracellular glucose concentration failed to facilitate LTP  and application of an insulin-responsive glucose transporter-4 inhibitor  did not impair the effect of insulin. These results suggest that the  facilitatory action of insulin on LTP is not an indirect effect on  glucose homeostasis/utilization. Involvement of the MAPK/ERK pathway, a  known downstream pathway of insulin signaling, was revealed by  pretreatment with PD98059, which blocked the insulin-mediated LTP  facilitation. Consistent with this, high-frequency stimulation induced a  significant increase in the level of phosphorylated Erk-2 in  insulin-treated hippocampus. Taken together, these results suggest that  insulin may be an essential factor in the immature brain, allowing the expression of LTP to facilitate learning and memory.