细胞外信号调节激酶在前扣带回皮层的激活有助于诱导大鼠的长时程增强。
Activation of extracellular signal-regulated kinase in the anterior cingulate cortex contributes to the induction of long-term potentiation in rats.
机构信息
Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
出版信息
Neurosci Bull. 2009 Oct;25(5):301-8. doi: 10.1007/s12264-009-0904-5.
OBJECTIVE
To 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.
METHODS
LTP of field potential was recorded in ACC slice and the expressions of phospho-ERK (pERK) and phospho-CREB (pCREB) were examined using immunohistochemistry method.
RESULTS
LTP 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 micromol/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.
CONCLUSION
NMDA receptor and ERK-CREB pathway are necessary for the induction of LTP in rat ACC and may play important roles in pain emotion.
目的
探讨细胞外信号调节激酶（ERK）/环磷酸腺苷反应元件结合蛋白（CREB）通路在扣带前皮质（ACC）长时程增强（LTP）诱导中的作用，该作用可能与疼痛相关的负性情绪有关。
方法
在 ACC 切片中记录场电位 LTP，并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，100 Hz，1 s）可稳定诱导 ACC 切片中的 LTP，而 APv（NMDA 受体拮抗剂）可阻断 ACC 中 LTP 的诱导，表明该实验中的 LTP 依赖于 NMDA 受体。在强直刺激前 30 min 时，应用 PD98059（50 μmol/L，一种选择性 MEK 抑制剂）可完全阻断 LTP 的诱导。此外，LTP 诱导后，ACC 中的 pERK 蛋白水平短暂增加，在强直刺激后 5 min 开始，并在 1 h 后恢复基础水平。pCREB 的蛋白水平也在 LTP 诱导后增加。PD98059 预处理可阻断 pERK 和 pCREB 表达的上调。双重免疫染色显示，LTP 诱导后，大多数 pERK 与 pCREB 共定位。
结论
NMDA 受体和 ERK-CREB 通路是大鼠 ACC 中 LTP 诱导所必需的，可能在疼痛情绪中发挥重要作用。
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