Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium.
Histol Histopathol. 2010 Aug;25(8):975-84. doi: 10.14670/HH-25.975.
Important physiological functions of neurotrophins (NTs) in airways and lungs are the early development, differentiation and maintenance of peripheral sensory neurons. The main pulmonary sensory innervation is of vagal origin, with several nerve fibre populations that selectively contact complex morphologically well-characterized receptor end-organs, called neuroepithelial bodies (NEBs). NEBs in mouse lungs are innervated by at least two separate myelinated vagal sensory nerve fibre populations, of which the neurochemical coding is suggestive of a mechanosensory function. Since neurotrophin-4 (NT-4) has been especially described to be important for the maintenance of mechanosensory nerve terminals, the present study aimed at investigating the NT-4 dependency of the two myelinated vagal sensory nerve fibre populations innervating mouse pulmonary NEBs. Multiple immunostaining in 21-day-old and adult mouse lungs revealed the expression of the NT-4 receptor TrkB on the two different myelinated vagal sensory nerve fibre populations, i.e., the vesicular glutamate transporter/calbindin-positive and the P2X2/3-positive fibres, which selectively contact pulmonary NEBs. Examination of the effect of the lack of NT-4 on these NEB-related nerve fibre populations, by comparing adult NT-4-/- and wild-type mice, revealed that in NT-4-/- mice the percentage of NEBs contacted by P2X2/3+ is reduced by 75%, while the VGLUT+/CB+ population seemed to be unaffected. This study demonstrated that although mouse pulmonary NEBs are contacted by two distinct TrkB expressing populations of vagal myelinated afferents, only one is distinctly reduced in NT-4 deficient mice, suggesting the involvement of NTs. In view of the growing evidence for the involvement of NTs in neuronal plasticity associated with airway diseases, pulmonary NEBs innervated by NT-sensitive vagal afferents may play a significant role.
神经递质(NTs)在气道和肺部的重要生理功能是外周感觉神经元的早期发育、分化和维持。主要的肺感觉神经支配来自迷走神经,有几个神经纤维群体选择性地接触形态复杂、特征良好的受体终末器官,称为神经上皮体(NEBs)。小鼠肺部的 NEB 至少由两个独立的有髓迷走感觉神经纤维群体支配,其神经化学编码提示具有机械感觉功能。由于神经生长因子-4(NT-4)特别被描述为维持机械感觉神经末梢的重要物质,本研究旨在研究支配小鼠肺部 NEB 的两个有髓迷走感觉神经纤维群体对 NT-4 的依赖性。21 天龄和成年小鼠肺部的多重免疫染色显示,两种不同的有髓迷走感觉神经纤维群体,即囊泡谷氨酸转运体/钙结合蛋白阳性和 P2X2/3 阳性纤维,表达 NT-4 受体 TrkB,它们选择性地接触肺部 NEB。通过比较成年 NT-4-/-和野生型小鼠,研究缺乏 NT-4 对这些与 NEB 相关的神经纤维群体的影响,结果显示,在 NT-4-/-小鼠中,与 P2X2/3+接触的 NEB 比例减少了 75%,而 VGLUT+/CB+群体似乎没有受到影响。本研究表明,尽管小鼠肺部的 NEB 被两个不同的 TrkB 表达的迷走有髓传入纤维群体接触,但只有一个在 NT-4 缺陷小鼠中明显减少,提示 NTs 的参与。鉴于越来越多的证据表明 NTs 参与与气道疾病相关的神经元可塑性,受 NT 敏感的迷走传入纤维支配的肺部 NEB 可能发挥重要作用。