PMID- 32277855
OWN - NLM
STAT- MEDLINE
DCOM- 20210119
LR  - 20230615
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 34
IP  - 6
DP  - 2020 Jun
TI  - Cholinergic neuroplasticity in asthma driven by TrkB signaling.
PG  - 7703-7717
LID - 10.1096/fj.202000170R [doi]
AB  - Parasympathetic neurons in the airways control bronchomotor tone. Increased 
      activity of cholinergic neurons are mediators of airway hyperresponsiveness (AHR) 
      in asthma, however, mechanisms are not elucidated. We describe remodeling of the 
      cholinergic neuronal network in asthmatic airways driven by brain-derived 
      neurotrophic factor (BDNF) and Tropomyosin receptor kinase B (TrkB). Human 
      bronchial biopsies were stained for 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 
      (Ntrk2tm1Ddg/J) with impaired BDNF signaling were chronically exposed to 
      ovalbumin (OVA). Neuronal VAChT staining and airway narrowing in response to 
      electrical field stimulation in precision cut lung slices (PCLS) were assessed. 
      Increased cholinergic fibers in asthmatic airway biopsies was found, paralleled 
      by increased TrkB gene expression in human lung tissue, and SNPs in the NTRK2 
      [TrkB] and BDNF genes linked to asthma. Chronic allergen exposure in mice 
      resulted in increased density of cholinergic nerves, which was prevented by 
      inhibiting TrkB. Increased nerve density resulted in AHR in vivo and in increased 
      nerve-dependent airway reactivity in lung slices mediated via TrkB. These 
      findings show cholinergic neuroplasticity in asthma driven by TrkB signaling and 
      suggest that the BDNF-TrkB pathway may be a potential target.
CI  - (c) 2020 The Authors. The FASEB Journal published by Wiley periodicals LLC on 
      behalf of Federation of American Societies for Experimental Biology.
FAU - Dragunas, Guilherme
AU  - Dragunas G
AD  - Department of Molecular Pharmacology, University of Groningen, Groningen, the 
      Netherlands.
AD  - GRIAC Research Institute, University Medical Center Groningen, University of 
      Groningen, Groningen, the Netherlands.
AD  - Department of Pharmacology, University of Sao Paulo, Sao Paulo, Brazil.
FAU - Woest, Manon E
AU  - Woest ME
AD  - Department of Molecular Pharmacology, University of Groningen, Groningen, the 
      Netherlands.
AD  - GRIAC Research Institute, University Medical Center Groningen, University of 
      Groningen, Groningen, the Netherlands.
FAU - Nijboer, Susan
AU  - Nijboer S
AD  - Department of Molecular Pharmacology, University of Groningen, Groningen, the 
      Netherlands.
AD  - GRIAC Research Institute, University Medical Center Groningen, University of 
      Groningen, Groningen, the Netherlands.
FAU - Bos, Sophie T
AU  - Bos ST
AD  - Department of Molecular Pharmacology, University of Groningen, Groningen, the 
      Netherlands.
AD  - GRIAC Research Institute, University Medical Center Groningen, University of 
      Groningen, Groningen, the Netherlands.
FAU - van Asselt, Janet
AU  - van Asselt J
AD  - Department of Molecular Pharmacology, University of Groningen, Groningen, the 
      Netherlands.
AD  - GRIAC Research Institute, University Medical Center Groningen, University of 
      Groningen, Groningen, the Netherlands.
FAU - de Groot, Anne P
AU  - de Groot AP
AD  - Department of Molecular Pharmacology, University of Groningen, Groningen, the 
      Netherlands.
AD  - GRIAC Research Institute, University Medical Center Groningen, University of 
      Groningen, Groningen, the Netherlands.
FAU - Vohlidalova, Eva
AU  - Vohlidalova E
AD  - Department of Molecular Pharmacology, University of Groningen, Groningen, the 
      Netherlands.
AD  - GRIAC Research Institute, University Medical Center Groningen, University of 
      Groningen, Groningen, the Netherlands.
FAU - Vermeulen, Corneel J
AU  - Vermeulen CJ
AD  - GRIAC Research Institute, University Medical Center Groningen, University of 
      Groningen, Groningen, the Netherlands.
AD  - Department of Pulmonary Diseases, UMCG, Groningen, the Netherlands.
FAU - Ditz, Benedikt
AU  - Ditz B
AD  - GRIAC Research Institute, University Medical Center Groningen, University of 
      Groningen, Groningen, the Netherlands.
AD  - Department of Pulmonary Diseases, UMCG, Groningen, the Netherlands.
FAU - Vonk, Judith M
AU  - Vonk JM
AD  - GRIAC Research Institute, University Medical Center Groningen, University of 
      Groningen, Groningen, the Netherlands.
AD  - Department of Epidemiology, UMCG, Groningen, the Netherlands.
FAU - Koppelman, Gerard H
AU  - Koppelman GH
AD  - GRIAC Research Institute, University Medical Center Groningen, University of 
      Groningen, Groningen, the Netherlands.
AD  - Department of Pediatric Pulmonology and Pediatric Allergology, University Medical 
      Center Groningen, University of Groningen, Beatrix Children's Hospital, 
      Groningen, the Netherlands.
FAU - van den Berge, Maarten
AU  - van den Berge M
AD  - GRIAC Research Institute, University Medical Center Groningen, University of 
      Groningen, Groningen, the Netherlands.
AD  - Department of Pulmonary Diseases, UMCG, Groningen, the Netherlands.
FAU - Ten Hacken, Nick H T
AU  - Ten Hacken NHT
AD  - GRIAC Research Institute, University Medical Center Groningen, University of 
      Groningen, Groningen, the Netherlands.
AD  - Department of Pulmonary Diseases, UMCG, Groningen, the Netherlands.
FAU - Timens, Wim
AU  - Timens W
AD  - GRIAC Research Institute, University Medical Center Groningen, University of 
      Groningen, Groningen, the Netherlands.
AD  - Department of Pathology, UMCG, Groningen, the Netherlands.
FAU - Munhoz, Carolina D
AU  - Munhoz CD
AD  - Department of Pharmacology, University of Sao Paulo, Sao Paulo, Brazil.
FAU - Prakash, Y S
AU  - Prakash YS
AD  - Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, 
      MN, USA.
FAU - Gosens, Reinoud
AU  - Gosens R
AD  - Department of Molecular Pharmacology, University of Groningen, Groningen, the 
      Netherlands.
AD  - GRIAC Research Institute, University Medical Center Groningen, University of 
      Groningen, Groningen, the Netherlands.
FAU - Kistemaker, Loes E M
AU  - Kistemaker LEM
AD  - Department of Molecular Pharmacology, University of Groningen, Groningen, the 
      Netherlands.
AD  - GRIAC Research Institute, University Medical Center Groningen, University of 
      Groningen, Groningen, the Netherlands.
LA  - eng
GR  - R01 HL088029/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200411
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Cholinergic Agents)
RN  - 0 (Membrane Glycoproteins)
RN  - 9006-59-1 (Ovalbumin)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.1 (tropomyosin-related kinase-B, human)
SB  - IM
MH  - Adolescent
MH  - Animals
MH  - Asthma/*genetics
MH  - Case-Control Studies
MH  - Cholinergic Agents/*metabolism
MH  - Female
MH  - Humans
MH  - Inflammation/genetics
MH  - Lung/metabolism
MH  - Male
MH  - Membrane Glycoproteins/*genetics
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Muscle, Smooth/metabolism
MH  - Neuronal Plasticity/*genetics
MH  - Ovalbumin/genetics
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Receptor, trkB/*genetics
MH  - Signal Transduction/*genetics
PMC - PMC7302963
MID - NIHMS1585334
OTO - NOTNLM
OT  - asthma
OT  - lung innervation
OT  - neuroplasticity
OT  - neurotrophins
COIS- GD, MW, SN, SB, JA, AG, EV, CV, BD, JV, GH, MB, NH, WT, CM, and YP have no 
      conflict of interest. LK is the director of Aquilo BV and has received funding 
      for research and lecture fees from Boehringer Ingelheim. RG has received funding 
      for research and lecture fees from Boehringer Ingelheim.
EDAT- 2020/04/12 06:00
MHDA- 2021/01/20 06:00
PMCR- 2020/09/17
CRDT- 2020/04/12 06:00
PHST- 2020/01/22 00:00 [received]
PHST- 2020/03/23 00:00 [revised]
PHST- 2020/03/24 00:00 [accepted]
PHST- 2020/04/12 06:00 [pubmed]
PHST- 2021/01/20 06:00 [medline]
PHST- 2020/04/12 06:00 [entrez]
PHST- 2020/09/17 00:00 [pmc-release]
AID - FSB220507 [pii]
AID - 10.1096/fj.202000170R [doi]
PST - ppublish
SO  - FASEB J. 2020 Jun;34(6):7703-7717. doi: 10.1096/fj.202000170R. Epub 2020 Apr 11.