Induction of Inflammation in the Brain by Daily JUUL Aerosol Inhalation

Abstract

Introduction The use of electronic (e)-cigarettes has become increasingly popular over the years, with JUUL being one of the most popular devices. The effects of e-cigarettes on the body and overall health remain unknown. We assessed the effects of daily e-cigarette aerosol inhalation on the pathways of addiction in the brain, focusing on neuroinflammation. We focused on the nucleus accumbens core and shell (NAc-core and NAc-shell) as well as the hippocampus. The NAc-core and NAc-shell are regions in the brain that play a role in behavior modification, formation of drug reward behaviors, and formation of anxious or depressive behaviors. We hypothesized that, due to the highly addictive chemical nicotine and toxic/inflammatory chemicals contained within, chronic JUUL aerosol inhalation would lead to neuroinflammation within these areas. Methods C57BL/6 mice were exposed to either JUUL Mango or JUUL Mint (both containing 59 mg/mL nicotine) e-cigarette aerosols for 60 mins daily for 4-12 weeks. Mice were exposed for 20 minutes, 3 times a day, for 5 days a week. Control mice were exposed to room air alone. Exposures were conducted in the Scireq whole body inExpose System. Inflammatory biomarkers in the brain were assessed by quantitative PCR and Western blotting. Results At the end of 4 weeks exposure, mice exposed to JUUL Mango and JUUL Mint had significantly increased TNF-α in the NAc-core and NAc-shell (p < 0.01 and p < 0.001, respectively), with elevations in IL-1β as well (p <0.05). The NAc-shell also showed significantly increased IL-6 (p < 0.001) and HMGB-1 (p < 0.01) for both flavors. There were no significant changes in the hippocampus. At the end of 12 weeks exposure, there was significantly increased TNF-α in the NAc-core and NAc-shell for both Mint- (p < 0.01 and p < 0.001, respectively) and Mango-exposed JUUL mice (p < 0.05 and p < 0.01, respectively). The NAc-shell also showed significantly increased IL-1β, IL-6, HMGB-1, and RAGE at 12 weeks (p < 0.001, p < 0.01, p < 0.01, and p < 0.01, respectively), while the hippocampus showed significantly decreased HMGB-1 for both flavors (p < 0.05). Conclusions As evidenced by the significant increase in levels of proinflammatory cytokines within brain regions important for regulating drug reward behaviors and mood, our data suggest that chronic JUUL aerosol inhalation induces neuroinflammation and puts users at risk for anxiety, depression, and heightened drug addiction. More work is needed to understand the impacts of e-cigarette use on both the central nervous system and health in general.