胰島素對幼鼠海馬長時程增強(LTP)表達的促進作用

Prof Yung WH/CUHK 香港中文大學

許多研究表明胰島素信號傳導失誤導致學習和記憶障礙。不過，以前的研究不能確定胰島素跟長時程增強 (LTP)的關聯，雖然LTP為記憶形成的最佳細胞模型。在這里我們顯示胰島素預處理對成年大鼠海馬長時程增強沒有影響，但能促進還沒成熟海馬 LTP 表達。酪氨酸激酶抑制劑 AG-1024能取消胰島素對幼鼠的影響， 所以胰島素受體可能涉及在這個過程內。另一方面， 增加細胞外葡萄糖濃度不能促進LTP， 加入對胰島素有作用的葡萄糖轉運蛋白 4 抑制劑 （insulin-responsive glucose transporter-4 inhibitor）不會降低胰島素的作用。這些結果表明胰島素對 LTP 的促進不是一個間接的 胰島素穩態/利用 機制。使用PD98059中斷胰島素介導 LTP ，得知胰島素信號下游途徑MAPK/ERK分子涉及在過程中。跟上述結果一致，高頻刺激胰島素處理海馬增加磷酸化 Erk-2 水平。綜上所述，這些研究結果表明胰島素可能是未成熟的腦中，一個非常重要的物質以便 LTP出現 加強腦部的學習

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.