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外周神经损伤后大鼠背根神经节细胞和脊髓中的神经肽表达,特别提及甘丙肽

Neuropeptide expression in rat dorsal root ganglion cells and spinal cord after peripheral nerve injury with special reference to galanin.

作者信息

Villar M J, Cortés R, Theodorsson E, Wiesenfeld-Hallin Z, Schalling M, Fahrenkrug J, Emson P C, Hökfelt T

机构信息

Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.

出版信息

Neuroscience. 1989;33(3):587-604. doi: 10.1016/0306-4522(89)90411-9.

Abstract

The temporal course of changes in peptide expression in the dorsal root ganglia L4 and L5 and in the dorsal horn of the spinal cord has been studied in rats subjected to a sciatic nerve transection at a mid-thigh level following different survival times. Galanin-, substance P-, vasoactive intestinal polypeptide-, peptide histidine-isoleucine- and calcitonin gene-related peptide-like immunoreactivities have been studied both by immunohistochemistry and radioimmunoassay. Galanin messenger ribonucleic acid has also been studied by in situ hybridization in the dorsal root ganglia of normal and lesioned animals. In addition, a group of animals with a sciatic nerve crush was studied to compare possible differences in peptide expression after both types of lesions. The results show that the transection induces an increase in the number of cell bodies expressing galanin-like immunoreactivity in the ganglia, and that the galanin levels rise about 120-fold after three and 14 days of survival. This increase reflected increased synthesis of the peptide, since there was a rise in the galanin messenger ribonucleic acid already at 24 h post-lesion, which was maintained for at least 60 days. In the spinal cord there was an increase of staining in the midportion of the outer layers of the dorsal horn that corresponded to fibers thought to arise from cells of the dorsal root ganglia affected by the transection. Also a depletion of substance P-like and an increase in vasoactive intestinal polypeptide- and peptide histidine-isoleucine-like immunoreactivities in the dorsal root ganglia were confirmed. These changes were shown to be rapidly detectable and were paralleled by similar changes in the dorsal horn of the spinal cord. For calcitonin gene-related peptide the immunohistochemistry was inconclusive, and the radioimmunoassay showed no detectable changes. After nerve crush a transient increase in the number of galanin immunoreactive neurons was observed, as well as a decrease in the number of neurons showing substance P-like immunoreactivity. These changes were most noticeable between six and 14 days of survival. After this, peptide expression seemed to return slowly to normal, that is by day 45 post-crush only a few cells showed galanin-like, and many sensory neurons expressed substance P-like immunoreactivity. The results demonstrate that when primary sensory neurons are peripherally lesioned they respond in a complex manner, altering their normal production of peptides by increasing or decreasing their synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

在不同存活时间后,对在大腿中部水平进行坐骨神经横断的大鼠,研究了其L4和L5背根神经节以及脊髓背角中肽表达变化的时间进程。通过免疫组织化学和放射免疫测定法研究了甘丙肽、P物质、血管活性肠多肽、肽组氨酸异亮氨酸和降钙素基因相关肽样免疫反应性。还通过原位杂交在正常和损伤动物的背根神经节中研究了甘丙肽信使核糖核酸。此外,研究了一组坐骨神经挤压伤动物,以比较两种损伤后肽表达的可能差异。结果表明,横断诱导神经节中表达甘丙肽样免疫反应性的细胞体数量增加,并且在存活3天和14天后甘丙肽水平升高约120倍。这种增加反映了该肽合成的增加,因为在损伤后24小时甘丙肽信使核糖核酸就已经升高,并持续至少60天。在脊髓中,背角外层中部的染色增加,这与被认为起源于受横断影响的背根神经节细胞的纤维相对应。还证实了背根神经节中P物质样免疫反应性的减少以及血管活性肠多肽和肽组氨酸异亮氨酸样免疫反应性的增加。这些变化显示可快速检测到,并且在脊髓背角中也有类似变化。对于降钙素基因相关肽,免疫组织化学结果不明确,放射免疫测定未显示可检测到的变化。神经挤压伤后,观察到甘丙肽免疫反应性神经元数量短暂增加,以及显示P物质样免疫反应性的神经元数量减少。这些变化在存活6天至14天之间最为明显。此后,肽表达似乎缓慢恢复正常,即挤压伤后45天时只有少数细胞显示甘丙肽样免疫反应性,许多感觉神经元表达P物质样免疫反应性。结果表明,当初级感觉神经元在周围受到损伤时,它们会以复杂的方式做出反应,通过增加或减少合成来改变其正常的肽产生。(摘要截断于400字)

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