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The effects of chronic unpredictable stress on the neuroplasticity and inflammation in the airways of a murine model of allergic Asthma

Grant number: 17/16549-2
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): June 01, 2018
Effective date (End): February 10, 2022
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Carolina Demarchi Munhoz
Grantee:Guilherme Dragunas
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):18/18762-8 - Stressing the lungs: neuronal plasticity in allergic airway inflammation, BE.EP.DD

Abstract

Recent data show the growing number of people living chronically with stress and indicate the need of studying the effects of this exposure. Asthma represents a major burden for the world health and generates large public expenses with its treatment. There is a clear association between chronic stresses and worsening of Asthma symptoms, however, mechanisms that explain how prolonged glucocorticoid exposure mediates this effect are still poorly understood. It is known that in allergic Asthma there may be a disorder in the autonomic and sensory innervation in the airways, partly explained by the paracrine secretion of neurotrophins, contributing to the pathophysiology of the disease. Chronic stress seems to contribute to the increased secretion of these neurotrophins and this may be conditioned by a change in the notably anti-inflammatory glucocorticoid signaling in Asthma.In this study we will investigate the repercussion of the exposure to chronic unpredictable stress on allergic pulmonary inflammation in Balb/c mice. Therefore, after theexposure to 12 days of unpredictable stress, the animals will be sensitized with ovalbumin (OVA) associated with alum. 24 h after the last challenge, neuronal functional activity in the airways by Electric Field Stimulation in organotypic cultures, as well as in vivo reactivity in response to methacholine will be evaluated. The pulmonary inflammatory phenotype, concentration of neurotrophins, and neuronal plasticity will be investigated in samples from the bronchoalveolar lavage, pulmonary lobes and dorsal root ganglia of these animals. Finally, the participation of glucocorticoid signaling via its receptor, GR, will be studied as well. (AU)