Brain‐derived neurotrophic factor (BDNF) contributes to neuronal dysfunction in a model of allergic airway inflammation

Braun, Armin; Lommatzsch, Marek; Neuhaus-Steinmetz, Ulrich; Quarcoo, David; Glaab, Thomas; McGregor, G.P.; Fischer, Axel; Renz, Harald

doi:10.1038/sj.bjp.0705638

Cited by 93 publications

(83 citation statements)

References 48 publications

(93 reference statements)

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“…Although the present study is the first to report an allergeninduced production of GDNF in the airways, others have noted that allergic inflammation is associated with elevations in BDNF production (5,6). This finding is not limited to laboratory animals.…”

Section: Discussionmentioning

confidence: 54%

TRPV1 induction in airway vagal low-threshold mechanosensory neurons by allergen challenge and neurotrophic factors

Lieu

Myers

Meeker

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

112

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Lieu T, Myers AC, Meeker S, Undem BJ. TRPV1 induction in airway vagal low-threshold mechanosensory neurons by allergen challenge and neurotrophic factors. Am J Physiol Lung Cell Mol Physiol 302: L941-L948, 2012. First published March 2, 2012; doi:10.1152/ajplung.00366.2011.-We addressed the hypothesis that allergic inflammation in guinea pig airways leads to a phenotypic switch in vagal tracheal cough-causing, low-threshold mechanosensitive A␦ neurons, such that they begin expressing functional transient receptor potential vanilloid (TRPV1) channels. Guinea pigs were actively sensitized to ovalbumin (OVA) and beginning 21 days later exposed via aerosol to OVA daily for 3 days. Tracheal-specific neurons were identified in the nodose ganglion using retrograde tracing techniques. Tracheal specific neurons were isolated, and mRNA expression was evaluated at the single-neuron level using RT-PCR analysis. Electrophysiological studies have revealed that the vast majority of vagal nodose afferent nerves innervating the trachea are capsaicin-insensitive A␦-fibers. Consistent with this, we found Ͻ20% of these neurons express TRPV1 mRNA or respond to capsaicin in a calcium assay. Allergen exposure induced de novo TRPV1 mRNA in a majority of the tracheal-specific nodose neurons (P Ͻ 0.05). The allergen-induced TRPV1 induction was mimicked by applying either brain-derived neurotrophic factor (BDNF) or glialderived neurotrophic factor (GDNF) to the tracheal lumen. The BDNF-induced phenotypic change observed at the level of mRNA expression was mimicked using a calcium assay to assess functional TRPV1 ion channels. Finally, OVA exposure induced BDNF and GDNF production in the tracheal epithelium, the immediate vicinity of the nodose A␦ -fibers terminations. The induction of TRPV1 in nodose tracheal A␦ -fibers would substantively expand the nature of stimuli capable of activating these cough-causing nerves. asthma; C-fiber; capsaicin; vagus IN THE SOMATOSENSORY SYSTEM, inflammation can lead to a so-called phenotypic switch in which low-threshold touchsensitive mechanosensitive A␤-fibers take on a nociceptor phenotype by expressing de novo substance P, a neuropeptide typically limited to C-fiber neurons. When substance P is released from the central terminals of the A␤-fibers upon light touch, the excitability of spinal cord neurons is increased, leading to the hypothesis that the phenotypic switch may contribute to the phenomenon of allodynia (21). We have noted that allergic inflammation of the respiratory tract leads to a similar phenotypic change in low-threshold vagal nodose mechanosensory neurons innervating the lung (8) and trachea (19), such that they express substance P and calcitonin generelated peptide (CGRP), neuropeptides typically limited to C-fibers in these tissues (and a subset of jugular A␦-fibers in the trachea) (24). Zhang et al. (31) have extended the idea of a phenotypic switch by showing that transient receptor potential vanilloid (TRPV1), a key ion channel limited to nociceptors in healthy airways, was ex...

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Section: Discussionmentioning

confidence: 54%

TRPV1 induction in airway vagal low-threshold mechanosensory neurons by allergen challenge and neurotrophic factors

Lieu

Myers

Meeker

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

112

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“…The chicken anti-BDNF antibody from Promega has been shown to be neutralizing and specific for BDNF (Braun et al 2004;Chen et al 2005;Zhu et al 2010;Shichinohe et al 2014). Briefly, C57BL/6J mice were anaesthetized with pentobarbital sodium and placed in a stereotaxic frame.…”

Section: Intracerebroventricular Infusions Of Anti-bdnf Antibodymentioning

confidence: 99%

WY14643 produces anti-depressant-like effects in mice via the BDNF signaling pathway

et al. 2014

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“…The relevance of such effects lies in the recent recognition that circulating and local BDNF concentrations, as well as receptor expression, are increased in asthma (22,44). Furthermore, animal studies suggest a role for BDNF in airway inflammation, remodeling, and hyperreactivity (47,48).…”

Section: Neurotrophins and Asmmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor in Cigarette Smoke–Induced Airway Hyperreactivity

Sathish¹,

VanOosten²,

Miller³

et al. 2013

Am J Respir Cell Mol Biol

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Enhanced airway smooth muscle (ASM) contractility contributes to increased resistance to airflow in diseases such as bronchitis and asthma that occur in passive smokers exposed to secondhand smoke. Little information exists on the cellular mechanisms underlying such airway hyperreactivity. Sputum samples of patients with chronic sinusitis, bronchitis, and asthma show increased concentrations of growth factors called neurotrophins, including brain-derived growth factor (BDNF), but their physiological significance remains unknown. In human ASM, we tested the hypothesis that BDNF contributes to increased contractility with cigarette smoke exposure. The exposure of ASM to 1% or 2% cigarette smoke extract (CSE) for 24 hours increased intracellular calcium ([Ca 21 ] i ) responses to histamine, and further potentiated the enhancing effects of a range of BDNF concentrations on such histamine responses. CSE exposure increased the expression of the both high-affinity and lowaffinity neurotrophin receptors tropomyosin-related kinase (Trk)-B and p75 pan-neurotrophin receptor, respectively. Quantitative ELISA showed that CSE increased BDNF secretion by human ASM cells. BDNF small interfering (si)RNA and/or the chelation of extracellular BDNF, using TrkB-fragment crystallizable, blunted the effects of CSE on [Ca 21 ] i responses as well as the CSE enhancement of cell proliferation, whereas TrkB siRNA blunted the effects of CSE on ASM contractility. These data suggest that cigarette smoke is a potent inducer of BDNF and TrkB expression and signaling in ASM, which then contribute to cigarette smoke-induced airway hyperresponsiveness.Keywords: neurotrophin; asthma; TrkB; environmental tobacco exposure; secondhand smoke Airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) can be triggered or exacerbated by cigarette smoke and secondhand smoke exposure (1-4). Furthermore, in people with preexisting airway diseases such as asthma, acute exposure to cigarette smoke can produce a bronchospastic response. Considerable evidence already exists that airway inflammation occurs with cigarette smoke exposure, and contributes to airway disease even in passive smokers. Regardless of the underlying causes for airway inflammation (of which there are many), increased airway smooth muscle (ASM) contractility is certainly a key factor contributing to the pathological airway narrowing and increased airflow resistance observed in asthma and bronchitis. Although smoke exposure is recognized to increase airway contractility, the mechanisms by which cigarette smoke enhances ASM contractility remain under investigation.In the nervous system, growth factors called neurotrophins (NTs) are well recognized for their role in the generation, growth, and maintenance of different neuronal populations (5-9). Both short-term (seconds or minutes) and long-term (hours or days) effects of NTs on nuclear and cytosolic signals have been recognized as favoring increased synaptic transmission and plasticity, cell proliferation, and surviva...

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Brain‐derived neurotrophic factor (BDNF) contributes to neuronal dysfunction in a model of allergic airway inflammation

Cited by 93 publications

References 48 publications

TRPV1 induction in airway vagal low-threshold mechanosensory neurons by allergen challenge and neurotrophic factors

TRPV1 induction in airway vagal low-threshold mechanosensory neurons by allergen challenge and neurotrophic factors

WY14643 produces anti-depressant-like effects in mice via the BDNF signaling pathway

Brain-Derived Neurotrophic Factor in Cigarette Smoke–Induced Airway Hyperreactivity

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