Chronic unpredictable stress exacerbates allergic airway inflammation in mice
G. Dragunas*1,2,3, M.A. de Oliveira1, W. T. de Lima1, R. Gosens2,3, C.D. Munhoz1
1- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo
2- Department of Molecular Pharmacology, University of Groningen
3 - Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen (UMCG), University of Groningen
It is accepted that psychological stress can lead to asthma exacerbations (1). Amid COVID-19 pandemic, exposure to chronic and, hence, deleterious forms of psychological stress has become usual. Stress can be classically defined as a real or potential threat to one’s homeostasis, generating physiological responses, such as HPA and SNS axis activation (2). Studies in the literature are widely in agreement that stress induces neuroplastic changes in psychiatric disorders and some suggest that this might also happen in conditions as asthma (3,4). However, the knowledge concerning how stress increases asthma severity and if neuronal mechanisms play a role are scarce.
We applied a 12 days chronic unpredictable stress (CUS) paradigm in OVA sensitized mice followed by two daily OVA challenges to induce allergic airway inflammation. 24h after the last challenge, mice had lung functional parameters analyzed, were euthanized, bronchoalveolar lavage collected and the lungs and dorsal root ganglia (DRG) harvested. The tissues were submitted to histological and molecular assays.
Exposure to 12 day-CUS increased cellular content recovered in BAL. This was paired to increased p65 NF-kB phosphorylation, TRPV1 and P2X3 receptors expression in DRG, but not in the lungs. Exposure to CUS before acute challenge to two OVA aerosol challenges significantly increased recovered cells in BAL. Opposite outcomes were observed after a single acute restraint stress (RS), as reduced cellularity in BAL and diminished airway resistance to methacholine. OVA+CUS group displayed increased NF-kB signaling and VCAM expression in the lungs.
Exposure to chronic stress can lead to allergic airway inflammation exacerbation in mice, whereas previous acute stress led to inflammation mitigation. Future experiments will determine differential cytokine and neurotrophic factor expression in the lungs and changes in innervation in the airways in response to chronic stress.
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