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Neurochemical and Ultrastructural Characterization of Unmyelinated Non-peptidergic C-Nociceptors and C-Low Threshold Mechanoreceptors Projecting to Lamina II of the Mouse Spinal Cord.
Cellular and Molecular Neurobiology ( IF 3.6 ) Pub Date : 2020-04-18 , DOI: 10.1007/s10571-020-00847-w
Chiara Salio 1 , Patrizia Aimar 1 , Pascale Malapert 2 , Aziz Moqrich 2 , Adalberto Merighi 1
Affiliation  

C-nociceptors (C-Ncs) and non-nociceptive C-low threshold mechanoreceptors (C-LTMRs) are two subpopulations of small unmyelinated non-peptidergic C-type neurons of the dorsal root ganglia (DRGs) with central projections displaying a specific pattern of termination in the spinal cord dorsal horn. Although these two subpopulations exist in several animals, remarkable neurochemical differences occur between mammals, particularly rat/humans from one side and mouse from the other. Mouse is widely investigated by transcriptomics. Therefore, we here studied the immunocytochemistry of murine C-type DRG neurons and their central terminals in spinal lamina II at light and electron microscopic levels. We used a panel of markers for peptidergic (CGRP), non-peptidergic (IB4), nociceptive (TRPV1), non-nociceptive (VGLUT3) C-type neurons and two strains of transgenic mice: the TAFA4Venus knock-in mouse to localize the TAFA4+ C-LTMRs, and a genetically engineered ginip mouse that allows an inducible and tissue-specific ablation of the DRG neurons expressing GINIP, a key modulator of GABABR-mediated analgesia. We confirmed that IB4 and TAFA4 did not coexist in small non-peptidergic C-type DRG neurons and separately tagged the C-Ncs and the C-LTMRs. We then showed that TRPV1 was expressed in only about 7% of the IB4+ non-peptidergic C-Ncs and their type Ia glomerular terminals within lamina II. Notably, the selective ablation of GINIP did not affect these neurons, whereas it reduced IB4 labeling in the medial part of lamina II and the density of C-LTMRs glomerular terminals to about one half throughout the entire lamina. We discuss the significance of these findings for interspecies differences and functional relevance.

中文翻译:

投射到小鼠脊髓 II 层的无髓鞘非肽能 C-伤害感受器和 C-低阈值机械感受器的神经化学和超微结构表征。

C-伤害性感受器 (C-Ncs) 和非伤害性 C-低阈值机械感受器 (C-LTMRs) 是背根神经节 (DRGs) 的小型无髓鞘非肽能 C 型神经元的两个亚群,中央投射显示特定模式终止于脊髓背角。尽管这两个亚群存在于几种动物中,但哺乳动物之间存在显着的神经化学差异,尤其是一侧的大鼠/人类和另一侧的小鼠。小鼠被转录组学广泛研究。因此,我们在这里研究了小鼠 C 型 DRG 神经元及其在光和电子显微镜水平上的脊髓椎板 II 中枢末端的免疫细胞化学。我们使用了一组肽能 (CGRP)、非肽能 (IB4)、伤害性 (TRPV1)、非伤害性 (VGLUT3) C 型神经元和两种转基因小鼠品系:用于定位 TAFA4+ C-LTMR 的 TAFA4Venus 敲入小鼠,以及允许对 DRG 神经元进行诱导性和组织特异性消融的基因工程 ginip 小鼠表达 GINIP,GABABR 介导的镇痛的关键调节剂。我们证实 IB4 和 TAFA4 在小的非肽能 C 型 DRG 神经元中不共存,并分别标记了 C-Ncs 和 C-LTMR。然后我们表明 TRPV1 仅在约 7% 的 IB4+ 非肽能 C-Ncs 及其 Ia 型肾小球末端在 II 层中表达。值得注意的是,GINIP 的选择性消融不影响这些神经元,而它减少了 IB4 标记在椎板 II 的内侧部分和 C-LTMRs 肾小球末端的密度在整个椎板中减少到大约一半。
更新日期:2020-04-20
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