Activation of extracellular signal-regulated kinase in the anterior cingulate cortex contributes to the induction of long-term potentiation in rats
Activation of extracellular signal-regulated kinase in the anterior cingulate cortex contributes to the induction of long-term potentiation in rats
复制标题
前扣带皮层细胞外信号调节激酶的激活有助于诱导大鼠长时程增强
DOI：
10.1007/s12264-009-0904-5
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发表时间：
2009-10-01
影响因子：
5.6
通讯作者：
Zhang, Yu-Qiu
中科院分区：
文献类型：
--
作者：
Cao, Hong;Cui, Yi-Hui;Zhang, Yu-Qiu
目的探讨细胞外信号调节蛋白(ERK)/cAMP反应元件结合蛋白(CREB)通路在前扣带回脑片长时程增强(LTP)诱导中的作用。方法在前扣带回脑片记录场电位LTP，用免疫组织化学方法检测磷酸化ERK(PERK)和磷酸化CREB(PCREB)的表达。结果高频刺激(2串、10 0 Hz、1 S)可稳定地诱导前扣带回脑片长时程增强，N-甲基-D-天冬氨酸受体拮抗剂APV可阻断长时程增强的诱导提示本实验中的LTP是NMDA受体依赖性的。强直刺激前30min应用选择性肌醇激酶抑制剂PD98059(50μ/L)可完全阻断长时程增强的诱导。此外，在LTP诱导后，ACC中PERK的蛋白水平一过性升高，在强直刺激后5min开始升高，1h恢复到基础水平。LTP诱导后，pCREB蛋白水平也明显升高。PD98059可阻断PERK和pCREB表达的上调。免疫组织化学双重染色显示，LTP诱导后大部分PERK与pCREB共定位。结论NMDA受体和ERK-CREB通路是大鼠ACC诱导LTP所必需的，可能在疼痛情绪中起重要作用。
ObjectiveTo explore the role of the extracellular signal-regulated kinase (ERK)/cAMP response element binding protein (CREB) pathway in the induction of long-term potentiation (LTP) in the anterior cingulate cortex (ACC) that may be implicated in pain-related negative emotion.MethodsLTP of field potential was recorded in ACC slice and the expressions of phospho-ERK (pERK) and phospho-CREB (pCREB) were examined using immunohistochemistry method.ResultsLTP could be induced stably in ACC slice by high frequency stimulation (2-train, 100 Hz, 1 s), while APv (an antagonist of NMDA receptor) could block the induction of LTP in the ACC, indicating that LTP in this experiment was NMDA receptor-dependent. Bath application of PD98059 (50 μmol/L), a selective MEK inhibitor, at 30 min before tetanic stimulation could completely block the induction of LTP. Moreover, the protein level of pERK in the ACC was transiently increased after LTP induction, starting at 5 min and returning to basal at 1 h after tetanic stimulation. The protein level of pCREB was also increased after LTP induction. The up-regulation in pERK and pCREB expressions could be blocked by pretreatment of PD98059. Double immunostaining showed that after LTP induction, most pERK was co-localized with pCREB.ConclusionNMDA receptor and ERK-CREB pathway are necessary for the induction of LTP in rat ACC and may play important roles in pain emotion.