Abstract
Allergic asthma is characterized by chronic airway inflammation and is constantly associated with anxiety disorder. Recent studies showed bidirectional interaction between the brain and the lung tissue. However, where and how the brain is affected in allergic asthma remains unclear. We aimed to investigate the neuroinflammatory, neurochemical, and neurometabolic alterations that lead to anxiety-like behavior in an experimental model of allergic asthma. Mice were submitted to an allergic asthma model induced by ovalbumin (OVA) and the control group received only Dulbecco’s phosphate-buffered saline (DPBS). Our findings indicate that airway inflammation increases interleukin (IL) -9, IL-13, eotaxin, and IL-1β release and changes acetylcholinesterase (AChE) and Na+,K+-ATPase activities in the brain of mice. Furthermore, we demonstrate that a higher reactive oxygen species (ROS) formation and antioxidant defense alteration that leads to protein damage and mitochondrial dysfunction. Therefore, airway inflammation promotes a pro-inflammatory environment with an increase of BDNF expression in the brain of allergic asthma mice. These pro-inflammatory environments lead to an increase in glucose uptake in the limbic regions and to anxiety-like behavior that was observed through the elevated plus maze (EPM) test and downregulation of glucocorticoid receptor (GR). In conclusion, the present study revealed for the first time that airway inflammation induces neuroinflammatory, neurochemical, and neurometabolic changes within the brain that leads to anxiety-like behavior. Knowledge about mechanisms that lead to anxiety phenotype in asthma is a beneficial tool that can be used for the complete management and treatment of the disease.
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Funding
This study was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, 23038.008562/2010–50) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, 460037/2014–5), Brazil.
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Géssica Luana Antunes: Conceptualization, Methodology, Formal analysis, Investigation, Writing—original draft, Writing—review & editing, Visualization. Josiane Silva Silveira: Conceptualization, Methodology, Investigation, Visualization. Carolina Luft: Conceptualization, Methodology, Investigation, Visualization. Samuel Greggio: Methodology, Investigation. Gianina Teribele Venturin: Methodology, Investigation. Felipe Schmitz: Investigation, Formal analysis. Helena Biasibetti-Brendler: Investigation, Formal analysis. Francieli Vuolo: Investigation. Felipe Dal-Pizzol: Investigation. Jaderson Costa da Costa: Investigation, Resources. Angela T. S. Wyse: Investigation, Resources, Supervision. Paulo Márcio Pitrez: Conceptualization, Formal analysis, Investigation, Writing—review & editing, Resources. Aline Andrea da Cunha: Conceptualization, Methodology, Formal analysis, Investigation, Writing—original draft, Writing—review & editing, Resources, Supervision, Project administration, Funding acquisition.
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Antunes, G.L., Silveira, J.S., Luft, C. et al. Airway inflammation induces anxiety-like behavior through neuroinflammatory, neurochemical, and neurometabolic changes in an allergic asthma model. Metab Brain Dis 37, 911–926 (2022). https://doi.org/10.1007/s11011-022-00907-8
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DOI: https://doi.org/10.1007/s11011-022-00907-8