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交感神经损伤对小鼠颈上交感神经节卫星胶质细胞的影响。

The effects of sympathetic nerve damage on satellite glial cells in the mouse superior cervical ganglion.

机构信息

Laboratory of Experimental Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem 91240, Israel; Faculty of Medicine, Hebrew University of Jerusalem, Israel.

Laboratory of Experimental Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem 91240, Israel; Faculty of Medicine, Hebrew University of Jerusalem, Israel.

出版信息

Auton Neurosci. 2019 Nov;221:102584. doi: 10.1016/j.autneu.2019.102584. Epub 2019 Aug 24.

DOI:10.1016/j.autneu.2019.102584
PMID:31494528
Abstract

Neurons in sensory, sympathetic, and parasympathetic ganglia are surrounded by satellite glial cell (SGCs). There is little information on the effects of nerve damage on SGCs in autonomic ganglia. We studied the consequences of damage to sympathetic nerve terminals by 6-hydroxydopamine (6-OHDA) on SGCs in the mouse superior cervical ganglia (Sup-CG). Immunostaining revealed that at 1-30 d post-6-OHDA injection, SGCs in Sup-CG were activated, as assayed by upregulation of glial fibrillary acidic protein. Intracellular labeling showed that dye coupling between SGCs around different neurons increased 4-6-fold 1-14 d after 6-OHDA injection. Behavioral testing 1-7 d post-6-OHDA showed that withdrawal threshold to tactile stimulation of the hind paws was reduced by 65-85%, consistent with hypersensitivity. A single intraperitoneal injection of the gap junction blocker carbenoxolone restored normal tactile thresholds in 6-OHDA-treated mice, suggesting a contribution of SGC gap junctions to pain. Using calcium imaging we found that after 6-OHDA treatment responses of SGCs to ATP were increased by about 30% compared with controls, but responses to ACh were reduced by 48%. The same experiments for SGCs in trigeminal ganglia from 6-OHDA injected mice showed no difference from controls, confirming that 6-OHDA acted selectively on sympathetic nerves. However, systemic inflammation induced by lipopolysaccharide did not affect SGCs of Sup-CG, but did influence SGCs in trigeminal ganglia in the same manner as 6-OHDA did on SGCs in Sup-CG. We conclude that even though SGCs in sympathetic and sensory ganglia are morphologically similar, they are quite different functionally, particularly after damage.

摘要

感觉神经、交感神经和副交感神经节中的神经元被卫星胶质细胞(SGCs)包围。关于神经损伤对自主神经节中 SGCs 的影响,我们知之甚少。我们研究了 6-羟多巴胺(6-OHDA)对小鼠颈上交感神经节(Sup-CG)中 SGCs 的交感神经末梢损伤的后果。免疫染色显示,在 6-OHDA 注射后 1-30 天,SGCs 被激活,通过胶质纤维酸性蛋白的上调来测定。细胞内标记显示,在 6-OHDA 注射后 1-14 天,不同神经元周围的 SGCs 之间的染料偶联增加了 4-6 倍。6-OHDA 注射后 1-7 天的行为测试表明,后爪触觉刺激的退缩阈值降低了 65-85%,表明存在超敏反应。单次腹腔注射缝隙连接阻滞剂 carbenoxolone 可使 6-OHDA 处理的小鼠恢复正常触觉阈值,表明 SGC 缝隙连接对疼痛有贡献。使用钙成像,我们发现与对照组相比,6-OHDA 处理后 SGC 对 ATP 的反应增加了约 30%,但对 ACh 的反应降低了 48%。对来自注射 6-OHDA 的小鼠三叉神经节中的 SGCs 进行相同的实验,与对照组相比没有差异,证实 6-OHDA 对交感神经起选择性作用。然而,脂多糖引起的全身炎症不会影响 Sup-CG 的 SGCs,但以与 6-OHDA 对 Sup-CG 的 SGCs 相同的方式影响三叉神经节中的 SGCs。我们得出结论,即使交感神经和感觉神经节中的 SGCs 在形态上相似,但它们在功能上却有很大的不同,特别是在损伤后。

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