title: Neurotrophin-4 dependency of intraepithelial vagal sensory nerve terminals that selectively contact pulmonary NEBs in mice.
abstract: 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.
authors.affiliation: Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium.
authors.forename: Fusun
authors.initials: F
authors.lastname: Oztay
authors.forename: Inge
authors.initials: I
authors.lastname: Brouns
authors.forename: Isabel
authors.initials: I
authors.lastname: Pintelon
authors.forename: Marion
authors.initials: M
authors.lastname: Raab
authors.forename: Winfried
authors.initials: W
authors.lastname: Neuhuber
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Timmermans
authors.forename: Dirk
authors.initials: D
authors.lastname: Adriaensen
mesh_terms: D000818:Animals; D064026:Calbindins; D008168:Lung / Q000294:innervation* / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009411:Nerve Endings / Q000378:metabolism / Q000502:physiology*; D009412:Nerve Fibers / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D046568:Neuroepithelial Bodies / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism / Q000502:physiology; D012137:Respiratory System / Q000378:metabolism; D064030:S100 Calcium Binding Protein G; D011984:Sensory Receptor Cells
chemical_list: D064026:Calbindins; D009414:Nerve Growth Factors; D064030:S100 Calcium Binding Protein G; C073922:neurotrophin 4