Social instability during peri-adolescent asthma exacerbates airway inflammation but ameliorates anxiety-like behavior and prefrontal cortex expression of stress regulation genes in mice

Allergic asthma is the most common chronic health challenge for youth in the United States, and it occurs during a critical time in neurobiological development when stressors can have long-lasting effects on adult mental health and stress regulation. Prior research has shown that youth who experience asthma or social challenges are at increased risk for developing anxiety. To determine if chronic social changes during development exacerbate allergic asthma immune function, anxiety, and/or stress physiology, we used a mouse model to test the influences of youth allergen exposure and constantly changing social conditions (‘social instability’) on adult asthma- and anxiety-related behavior and physiology. During postnatal days 7–59, male and female BALB/cJ mice were repeatedly exposed to house dust mite extract (HDM) to cause airway inflammation and/or to repeat cycles of social isolation and reorganization to simulate social instability. In adulthood, we measured basal asthma- and inflammation-related cytokines in circulation and lung gene expression, baseline and reactive circulating corticosterone (CORT), anxiety-like behavior, and hypothalamic–pituitary–adrenal (HPA) axis/anxiety-related gene expression in prefrontal cortex (PFC) and hypothalamus. Social instability decreased adult basal circulating CORT and GR expression in PFC and increased circulating CORT reactivity. In allergen-exposed mice, social instability exacerbated circulating cytokine concentrations and lung gene expression, and exacerbated female CORT responses to an acute stressor. But social instability negated female HDM-induced anxiety-like behavior and PFC FKBP5 gene expression. Results suggest that repeated social change (or repeated activation of the HPA) during adolescence decreases prefrontal sensitivity to glucocorticoids to produce adults that are resilient to anxiety in the context of allergic asthma.