Activation of glutamate transporters in the locus coeruleus paradoxically activates descending inhibition in rats.
Activation of glutamate transporters in the locus coeruleus paradoxically activates descending inhibition in rats.
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DOI：
10.1016/j.brainres.2009.12.086
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发表时间：
2010-03-04
期刊：
影响因子：
2.9
通讯作者：
Eisenach, James C.
中科院分区：
文献类型：
--
作者：
Hayashida, Ken-ichiro;Parker, Renee A.;Eisenach, James C.
去甲肾上腺素能下降抑制是一种重要的内源性疼痛缓解机制，可以通过局部谷氨酸信号传导激活。在本研究中，我们检查了利鲁唑激活谷氨酸转运蛋白对蓝斑（LC）神经元活性调节的影响，蓝斑（LC）神经元向脊髓提供主要的抑制性下行去甲肾上腺素能投射。 L5-L6 脊神经结扎 (SNL) 后，向 LC 中局部注射利鲁唑可剂量依赖性地降低大鼠的超敏反应。 LC注射利鲁唑的这种抗过敏作用可通过鞘内注射α2-肾上腺素受体拮抗剂伊达唑生和LC内共注射AMPA拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX）和间隙连接阻滞剂卡苯索隆（CBX）和LC内联合注射来阻断。 甲氯芬那酸（MEC）。在正常大鼠的脑干切片中，利鲁唑增加了 LC 中含有多巴胺-β-羟化酶 (DβH) 的细胞中表达磷酸化 cAMP 反应元件结合蛋白 (pCREB) 的细胞核。 CNQX 和 CBX 也可阻断 LC 神经元中利鲁唑诱导的 pCREB 激活。在原代星形胶质细胞培养物中，利鲁唑增强谷氨酸诱导的谷氨酸释放。与预期相反，这些结果表明，LC 中谷氨酸转运蛋白的激活导致细胞外谷氨酸信号传导增加，可能是通过促进星形胶质细胞释放谷氨酸，以及激活 LC 神经元以诱导下行抑制，并且 LC 中谷氨酸转运蛋白的这种矛盾作用需要间隙连接。
Descending noradrenergic inhibition is an important endogenous pain-relief mechanism which can be activated by local glutamate signaling. In the present study, we examined the effect of glutamate transporter activation by riluzole in the regulation of activity of locus coeruleus (LC) neurons, which provide the major inhibitory descending noradrenergic projection to the spinal cord. Local injection of riluzole into the LC dose-dependently reduced hypersensitivity in rats after L5-L6 spinal nerve ligation (SNL). This anti-hypersensitivity effect of LC-injected riluzole was blocked by intrathecal administration of the α2-adrenoceptor antagonist idazoxan and intra-LC co-injection of the AMPA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the gap-junction blockers, carbenoxolone (CBX) and meclofenamic acid (MEC). In brainstem slices from normal rats, riluzole increased phosphorylated cAMP response element binding protein (pCREB) expressing nuclei in dopamine-β-hydroxylase (DβH) containing cells in the LC. This riluzole-induced pCREB activation in LC neurons was also blocked by CNQX and CBX. In the primary astrocyte culture, riluzole enhanced glutamate-induced glutamate release. Contrary to expectations, these results suggest that activation of glutamate transporters in the LC results in increase of extracellular glutamate signaling, possibly via facilitation of glutamate release from astrocytes, and activation of LC neurons to induce descending inhibition, and that this paradoxical action of glutamate transporters in the LC requires gap-junction connections.
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GLT-1的基因转移是神经胶质谷氨酸转运蛋白，通过重组腺病毒衰减大鼠的炎症和神经性疼痛，将其转移到脊髓中。
影响因子：
3.3
作者：
Maeda S;Kawamoto A;Yatani Y;Shirakawa H;Nakagawa T;Kaneko S
通讯作者：
Kaneko S
影响因子：
4.2
作者：
Albo, F;Pieri, M;Zona, C
通讯作者：
Zona, C
影响因子：
4.2
作者：
Hansson, E;Muyderman, H;Rönnbäck, L
通讯作者：
Rönnbäck, L
影响因子：
8.8
作者：
Hayashida, Ken-ichiro;Obata, Hideaki;Eisenach, James C.
通讯作者：
Eisenach, James C.
影响因子：
4.7
作者：
Rojas, Hector;Colina, Claudia;DiPolo, Reinaldo
通讯作者：
DiPolo, Reinaldo