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甘丙肽受体2基因敲除小鼠的感觉神经元表型:聚焦于背根神经节神经元发育和疼痛行为

Sensory neuronal phenotype in galanin receptor 2 knockout mice: focus on dorsal root ganglion neurone development and pain behaviour.

作者信息

Shi Tie-Jun Sten, Hua Xiao-Ying, Lu Xiaoying, Malkmus Shelle, Kinney Jeff, Holmberg Kristina, Wirz Sebastian, Ceccatelli Sandra, Yaksh Tony, Bartfai Tamas, Hökfelt Tomas

机构信息

Department of Neuroscience, Karolinska Institutet, S171 77 Stockholm, Sweden.

出版信息

Eur J Neurosci. 2006 Feb;23(3):627-36. doi: 10.1111/j.1460-9568.2006.04593.x.

Abstract

Galanin is a 29-amino-acid peptide expressed in dorsal root ganglion (DRG) neurones and spinal dorsal horn neurones. It affects pain threshold and has developmental and trophic effects. Galanin acts at three G-protein-coupled receptors, galanin receptors (GalR1-3), each expressed in the DRGs as suggested by in situ hybridization and/or reverse transcriptase-polymerase chain reaction. The GalR2 knockout (-/-) mice permit studies on the contributions of this receptor subtype to the role of galanin at the spinal level. At 1 week after sciatic nerve transection (axotomy), there were 16-20% fewer neurones in intact and contralateral DRGs of -/- mice as compared with wild-type (WT) mice. In addition, a significant neurone loss (26% reduction) was found in the ipsilateral DRGs of WT mice, whereas no further neurone loss was seen in -/- mice. Expression of several peptides has been examined after axotomy, including galanin, neuropeptide Y and two of its receptors as well as substance P, and no significant differences were found between -/- and WT mice in either ipsi- or contralateral DRGs, respectively. After thermal injury and spinal nerve ligation, onset and duration of hyperalgesia in the injured paw were similar in GalR2-/- and WT animals. Recovery from spinal nerve ligation-caused allodynia had the same kinetics in -/- and WT animals. These data are in line with earlier observations from the peripheral and central nervous system, suggesting that galanin actions mediated by GalR2 subtype are of importance in neurodevelopment and neuroprotection.

摘要

甘丙肽是一种由29个氨基酸组成的肽,在背根神经节(DRG)神经元和脊髓背角神经元中表达。它会影响痛阈,并具有发育和营养作用。甘丙肽作用于三种G蛋白偶联受体,即甘丙肽受体(GalR1 - 3),原位杂交和/或逆转录聚合酶链反应表明,每种受体在DRG中均有表达。GalR2基因敲除(-/-)小鼠有助于研究该受体亚型在脊髓水平上对甘丙肽作用的贡献。坐骨神经横断(轴突切断)后1周,与野生型(WT)小鼠相比,-/-小鼠完整和对侧DRG中的神经元数量减少了16 - 20%。此外,在WT小鼠的同侧DRG中发现了显著的神经元损失(减少26%),而在-/-小鼠中未观察到进一步的神经元损失。轴突切断后,已经检测了几种肽的表达,包括甘丙肽、神经肽Y及其两种受体以及P物质,在-/-和WT小鼠的同侧或对侧DRG中均未发现显著差异。热损伤和脊髓神经结扎后,GalR2 -/-和WT动物受伤爪的痛觉过敏的发作和持续时间相似。-/-和WT动物从脊髓神经结扎引起的异常性疼痛中的恢复具有相同的动力学。这些数据与早期来自外周和中枢神经系统的观察结果一致,表明由GalR2亚型介导的甘丙肽作用在神经发育和神经保护中具有重要意义。

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