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The effects of e-cigarette use on organ systems across the body remain largely unknown. Nicotine, a primary component of the e-cigarette, is known to cause pulmonary inflammatory diseases, affect brain function, and activate carcinogenic pathways. The growing popularity of pod-based e-cigarettes including JUULTM motivated this study to define the effects of chronic JUUL aerosol inhalation on reward pathways in the brain and inflammation across organ systems. Female C57BL/6 mice were exposed to e-cigarette aerosols produced from JUUL Mango and Mint pods for 1 hour daily for 4-12 weeks using the InExpose system (Scireq). Half of the mice underwent acute lung injury (ALI) induction via intranasal challenge with E. coli lipopolysaccharide (LPS). Cardiopulmonary function was assessed, accompanied by blinded histologic grading of fibrosis in the kidneys, liver and heart. Inflammatory pathways in the brain, colon and heart were assessed by quantitative real-time PCR. Brains were also assessed for inflammatory changes by Western Blot. Chronic inhalation of JUUL aerosols induced inflammation in the brain reward regions at both 1 and 3 months, as evidenced by increased TNFα, IL-1β and IL-6 in the nucleus accumbens (Figure). In the colon, chronic inhalation of JUUL aerosols also drove increased expression of pro-inflammatory proteins (TNFα, IL-6, IL-8 and AMPKb1; Figure). Expression of pro-inflammatory genes in response to LPS challenge was upregulated in the heart (TNFα, IL-1β, IL-6, CCL2, CCL3, CXCL1 and CXCL2; Figure). Non-nicotine components of the vaping aerosols were found to …