Med64關(guān)于胰島素對(duì)幼鼠海馬LTP表達(dá)的研究

胰島素對(duì)幼鼠海馬長時(shí)程增強(qiáng)(LTP)表達(dá)的促進(jìn)作用

Prof Yung WH/CUHK 香港中文大學(xué)

許多研究表明胰島素信號(hào)傳導(dǎo)失誤導(dǎo)致學(xué)習(xí)和記憶障礙。不過，以前的研究不能確定胰島素跟長時(shí)程增強(qiáng) (LTP)的關(guān)聯(lián)，雖然LTP為記憶形成的最佳細(xì)胞模型。在這里我們顯示胰島素預(yù)處理對(duì)成年大鼠海馬長時(shí)程增強(qiáng)沒有影響，但能促進(jìn)還沒成熟海馬 LTP 表達(dá)。酪氨酸激酶抑制劑 AG-1024能取消胰島素對(duì)幼鼠的影響， 所以胰島素受體可能涉及在這個(gè)過程內(nèi)。另一方面， 增加細(xì)胞外葡萄糖濃度不能促進(jìn)LTP， 加入對(duì)胰島素有作用的葡萄糖轉(zhuǎn)運(yùn)蛋白 4 抑制劑 （insulin-responsive glucose transporter-4 inhibitor）不會(huì)降低胰島素的作用。這些結(jié)果表明胰島素對(duì) LTP 的促進(jìn)不是一個(gè)間接的 胰島素穩(wěn)態(tài)/利用 機(jī)制。使用PD98059中斷胰島素介導(dǎo) LTP ，得知胰島素信號(hào)下游途徑MAPK/ERK分子涉及在過程中。跟上述結(jié)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(jié)果表明胰島素可能是未成熟的腦中，一個(gè)非常重要的物質(zhì)以便 LTP出現(xiàn) 加強(qiáng)腦部的學(xué)習(xí)

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.