Mixed granulocytic airway inflammation impairs aversive learning and alters neuroimmune biomarkers in mice

Asthma is characterized by different phenotypes of airway inflammation, granulocytic cells may be recruited, both eosinophils and neutrophils. This pathology has been associated with behavioral alterations and neuroinflammation. The aim of the present study was to evaluate changes in behavior and neuroinflammation induced by mixed granulocytic chronic airway inflammation in male mice. Mice received injections of Saline (Control group) or ovalbumin (OVA group) plus Complete Freund's Adjuvant administered subcutaneously on day 0 followed by OVA nasal instillations on days 21, 22 and 23. On the 24 and 25rd, animals were evaluated in the plus-maze discriminative avoidance task to evaluate anxiety levels and motor activity concomitantly to the memory. Then, bronchoalveolar lavage (BALF), lung and brain structures were collected to perform ELISA to evaluate cytokines. In the brain, oxidative stress markers were also evaluated. OVA-challenged mice showed increased neutrophils and eosinophils recovered in BALF and the TNF-α levels quantified in the lung. OVA challenge increased TNF-α levels in cortex and hypothalamus, as well as I1-β and IL-6 levels in cortex and hippocampus. Moreover, OVA-challenged mice showed a deficit in aversive learning. Taken together our main results showed that mixed granulocytic chronic airway inflammation triggered neuroimmunomodulation, marked by increased pro-inflammatory cytokines in the prefrontal cortex, hippocampus and hypothalamus, and behavior changes, notably learning deficit.