Long-term potentiation of neuronal excitation by neuron-glia interactions in the rat spinal dorsal horn
Long-term potentiation of neuronal excitation by neuron-glia interactions in the rat spinal dorsal horn
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DOI：
10.1111/j.1460-9568.2007.05386.x
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发表时间：
2007-03-01
影响因子：
3.4
通讯作者：
Murase, Kazuyuki
中科院分区：
文献类型：
--
作者：
Ikeda, Hiroshi;Tsuda, Makoto;Murase, Kazuyuki
通过用电压敏感染料对大鼠脊髓切片中的神经元兴奋进行成像，我们研究了神经胶质细胞在P2 X受体激动剂α β-亚甲基ATP（α β meATP）触发的背角长时程增强（LTP）中的作用。浴应用α-β-meATP增强浅层背角神经元兴奋。P2 X受体拮抗剂TNP-ATP，PPADS和A-317491的存在下，增强被抑制，并没有诱导从大鼠脑片用辣椒素处理。这些结果表明，α β meATP作用于辣椒素敏感的初级传入终末的P2 X受体，可能是P2 X（3）和/或P2 X（2/3）。此外，神经胶质细胞代谢抑制剂一氟乙酸的处理抑制增强。用p38丝裂原活化蛋白激酶获得的结果（p38 MAPK）抑制剂SB 203580、肿瘤坏死因子-α（TNF-α）和白细胞介素（IL）-6，以及TNF-α和IL-6的抗体，以及通过用星形胶质细胞和小胶质细胞的标志物对活化的p38 MAPK进行双重免疫标记，证明α β meATP活化星形胶质细胞中的p38 MAPK，并且促炎细胞因子和p38 MAPK活化的存在对于α β meATP触发的LTP的诱导是必需的。这些发现表明，神经胶质细胞有助于α β-meATP诱导的LTP，这可能是诱导持续性疼痛的细胞机制的一部分。
By imaging neuronal excitation in rat spinal cord slices with a voltage-sensitive dye, we examined the role of glial cells in the P2X receptor agonist alpha beta-methylene ATP (alpha beta meATP)-triggered long-term potentiation (LTP) in the dorsal horn. Bath application of alpha beta meATP potentiated neuronal excitation in the superficial dorsal horn. The potentiation was inhibited in the presence of the P2X receptor antagonists TNP-ATP, PPADS and A-317491, and was not induced in slices taken from rats neonatally treated with capsaicin. These results suggest that alpha beta meATP acts on P2X receptors, possibly P2X(3) and/or P2X(2/3), in capsaicin-sensitive primary afferent terminals. Furthermore, the potentiation was inhibited by treatment with the glial metabolism inhibitor monofluoroacetic acid. Results obtained with the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580, tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6, and antibodies to TNF-alpha and IL-6, as well as by double immunolabelling of activated p38 MAPK with markers of astrocytes and microglia, demonstrated that alpha beta meATP activated p38 MAPK in astrocytes, and that the presence of proinflammatory cytokines and p38 MAPK activation were necessary for the induction of alpha beta meATP-triggered LTP. These findings indicate that glial cells contribute to the alpha beta meATP-induced LTP, which might be part of a cellular mechanism for the induction of persistent pain.