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Airborne Exposure to Fungal Allergens Elicits a Different Excitatory Synaptic Regulation Compared to Airborne Exposure to LPS in the Murine Brainstem Region Regulating Breathing

Abstract

We are using two modes of inflammation to trigger two different models of immune response: innate and adaptive immune responses. Using continuous exposure to aerosolized allergen, Alternaria alternata, triggers both innate and adaptive immunity, whereas using continuous aerosolized lipopolysaccharide (LPS) exposure triggers innate immunity only. Changes in the immunologic environment in the lung can communicate directly with the nucleus of the solitary tractus (NTS) in the medulla region. The response changes the synaptic plasticity among the neurons in NTS which may change physiological response of the breathing regulation under inflammatory conditions. Here, we are seeing how NTS changes its neuronal and glial cell plasticity as we expose mice to A. alternata (750μg/m3) and LPS (1μg/m3, 15μg/m3). We are quantifying the presynaptic protein terminals and second messenger signaling cascade mechanisms of medulla region of C57BL/6J mice after seven days of allergic and bacterial particulates. For signaling cascade analysis, we are using GeoMx Digital Spatial Profiler (DSP), a multiplex technology that reads 96 targets using the nCounter technology and used five panels of protein contents for cell signaling pathways: Neuronal core proteins, Glial subtypes, Autophagy, PI3K-AKT and MAPK signaling. Data analysis shows a decrease of co-localized vglut2 and synaptophysin puncta in A.alternata exposed females and an increase in higher dose LPS exposed females. There were no significant synaptic puncta co-localized regulation in neither exposed male mice. The protein analysis for the cascades shows different regulations of protein in both the exposed groups as well as between both sexes. In conclusion, the different models of inflammation suggest that female are having more synaptic regulation to the inflammations compared to males, however the signaling cascades remains differentially regulated and is sex specific.

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