Richard J Davidson, PhD – Slide of the Week

Richard J Davidson, PhD - Slide of the Week

Title: Molecular pathways connecting airway inflammation with changes in BOLD signal: a potential role for neuroinflammation

Legend: We sought to examine the molecular changes in the airway in asthma that connect inflammation with increased risk for depression and anxiety. We used functional MRI with an emotion-specific Stroop task in 28 individuals with mild asthma to measure changes in neural response following allergen provocation of airway inflammation. We measured changes in gene expression in cells gathered from bronchoalveolar lavage fluid and related these to changes in neural response, using a network analytic approach. Allergen challenge caused changes in gene expression in both the canonical Type 2 inflammatory pathway, as well as the Type 17 pathway, but it was the Type 17 pathway and related genes that showed the strongest relationship with changes in brain. These results shed light on the signaling pathways that may be most important in translating chronic airway inflammation into elevated risk for psychopathology, but they also hint at the possibility that the risks posed by airway inflammation may be more fundamental than psychopathology, impacting brain health more broadly, via neuroinflammatory mechanisms.

Citation: Citation: Altman, M.C., Dill-McFarland, K.A., Esnault, S., Jarjour, N.N., Busse, W.W. & Rosenkranz, M.A. (2023). Molecular pathways underlying lung-brain axis signaling in asthma: relevance for psychopathology and neuroinflammation. Journal of Allergy and Clinical Immunology. (in press)

Abstract: Background. Accumulating evidence indicates that asthma has systemic effects and impacts brain function. Although airway inflammation is proposed to initiate afferent communications with the brain, the signaling pathways have not been established. Objective: We sought to identify the cellular and molecular pathways involved in afferent lung to brain communication during airway inflammation in asthma. Methods: In twenty-three adults with mild asthma, segmental bronchial provocation with allergen (SBP-Ag) was used to provoke airway inflammation and retrieve bronchoalveolar lavage (BAL) fluid for targeted protein analysis and RNA-sequencing to determine gene-expression profiles. Neural responses to emotional cues in nodes of the salience network were assessed with functional magnetic resonance imaging at baseline and 48h post-SBP-Ag. Results: Cell deconvolution and gene co-expression network analysis identified 11 cell-associated gene modules that changed in response to SBP-Ag. SBP-Ag increased BAL eosinophils and expression of an eosinophil-associated module enriched for genes related to Th17-type inflammation (e.g., IL17A), as well as cell proliferation in lung and brain (e.g., NOTCH1, VEGFA, LIF). Increased expression of genes in this module, as well as several Th17-type inflammation-related proteins, was associated with an increase from baseline in salience network reactivity. Conclusions: Our results identify a specific inflammatory pathway linking asthma-related airway inflammation and emotion-related neural function. Systemically, Th17-type inflammation has been implicated in both depression and neuroinflammation, with impacts on long-term brain health. Thus, our data emphasize that inflammation in the lung in asthma may have profound effects outside of the lung that may be targetable with novel therapeutic approaches.

About the Lab: Research in Davidson’s laboratory is focused on the neural bases of disordered and healthy emotion and emotional style and methods to promote human flourishing, including meditation and related contemplative practices. His studies have included persons of all ages, from birth though old age, and have also included individuals with disorders of emotion, such as mood and anxiety disorders and autism, as well as expert meditation practitioners with tens of thousands of hours of experience. His research uses a wide range of methods, including different varieties of MRI, positron emission tomography, electroencephalography, and modern genetic and epigenetic methods.

Author: Melissa Rosenkranz, PhD

Investigator: Richard J Davidson, PhD

Slide of the Week Archives