Methods: Human bronchial biopsies were stained for the cholinergic marker vesicular acetylcholine transporter (VAChT). Human lung gene expression and single nucleotide polymorphisms (SNP) in neuroplasticity-related genes were compared between asthma and healthy patients. Wild-type (WT) and mutated TrkB knock-in mice (TrkBKI) with impaired BDNF signaling were chronically exposed to ovalbumin (OVA). Neuronal PGP9.5 and VAChT staining and airway narrowing in lung slices were assessed.
Results: Compared to healthy subjects, bronchial biopsies from asthma patients showed a 1.6 fold higher VAChT+ area. Human lung transcriptome analysis revealed TrkB gene expression 1.5 fold higher in asthma versus healthy. Moreover, 5 SNPs in the BDNF gene and 1 SNP in the TrkB gene were associated with asthma. WT mice displayed a 2.0 fold increase in PGP9.5 and 1.8 fold increase in VAChT+ area, which were not observed in TrkBKI. Furthermore, airway hyperresponsiveness, as seen in WT mice, was not observed in TrkBKI.
Conclusion: Our results indicate that in human asthma and in OVA exposed mice, an increased cholinergic nerve fiber density is present. The BDNF-TrkB signaling pathway might be involved in this neuroplasticity and genetic variation in both genes may contribute to asthma susceptibility.
|Tijdschrift||European Respiratory Journal|
|Nummer van het tijdschrift||63|
|Status||Published - 28-sep-2019|
|Evenement||ERS International congres 2019 - Madrid, Spain|
Duur: 28-sep-2019 → 2-okt-2019