Role of phosphorylation of ERK in induction and maintenance of LTP of the C‐fiber evoked field potentials in spinal dorsal horn
Role of phosphorylation of ERK in induction and maintenance of LTP of the C‐fiber evoked field potentials in spinal dorsal horn
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DOI：
10.1002/jnr.21013
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发表时间：
2006-10
影响因子：
4.2
通讯作者：
Wen-jun Xin;Qing-Juan Gong;Ji-Tian Xu;Hong-Wei Yang;Y. Zang;Tong Zhang;Yongyong Li;Xian-Guo Liu
中科院分区：
文献类型：
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作者：
Wen-jun Xin;Qing-Juan Gong;Ji-Tian Xu;Hong-Wei Yang;Y. Zang;Tong Zhang;Yongyong Li;Xian-Guo Liu
先前的研究表明，细胞外信号调节激酶(ERK)/cAMP反应元件结合蛋白（CREB）通路的激活对海马的长期增强（LTP）至关重要。本研究以成年大鼠为实验对象，研究了ERK/CREB通路在脊髓背角C纤维诱发场电位LTP中的作用，该LTP与病理性疼痛有关。Western blotting分析显示，同侧脊髓背角磷酸化ERK （p‐ERK）蛋白水平在LTP诱导后短暂升高，从15分钟开始，在破伤风刺激后60分钟恢复到对照，p‐CREB蛋白水平在30分钟升高，并在LTP诱导后持续至少3小时。双免疫荧光染色显示，LTP诱导后，p‐ERK和p‐CREB仅位于神经元中，而不位于脊髓背角的胶质细胞中。更重要的是，我们发现在破伤风刺激前30分钟脊髓应用选择性MEK抑制剂PD 98059 （100 μM）可阻断LTP诱导，并阻止脊髓背角p - ERK和p - CREB的增加。当在LTP诱导后15分钟应用时，PD98059逆转了已建立的LTP。然而，在LTP后30分钟给药时，该药物不影响脊髓LTP。我们的研究结果表明，脊髓背神经元ERK/CREB通路的激活对于诱导和维持C纤维诱发场电位的长期增强是必要的。©2006 Wiley‐Liss, Inc。
Previous works have shown that activation of extracellular signal‐regulated kinase (ERK)/cAMP response element binding protein (CREB) pathway is essential for long‐term potentiation (LTP) in hippocampus. In the present study, the role of the ERK/CREB pathway in LTP of C‐fiber evoked field potentials in spinal dorsal horn, which is relevant to pathologic pain, was investigated in adult rats. Western blotting analysis showed that the protein level of phosphorylated ERK (p‐ERK) in ipsilateral spinal dorsal horn was transiently increased after LTP induction, starting at 15 min and returning to control at 60 min after tetanic stimulation and that the protein level of p‐CREB increased at 30 min, persisting for at least 3 hr after LTP induction. Double immunofluorescence staining showed that p‐ERK and p‐CREB were only located in neurons but not in glial cells in the spinal dorsal horn after LTP induction. More importantly, we found that spinal application of PD 98059 (100 μM), a selective MEK inhibitor, at 30 min before tetanic stimulation blocked LTP induction and prevented the increase in p‐ERK and p‐CREB in spinal dorsal horn. When applied 15 min after LTP induction, PD98059 reversed established LTP. The drug, however, did not affect the spinal LTP, when applied at 30 min after LTP. Our results suggested that activation of ERK/CREB pathway in spinal dorsal neurons is necessary for induction and maintenance of long‐term potentiation of the C‐fiber evoked field potentials. © 2006 Wiley‐Liss, Inc.