UC San Diego

Traumatic brain injury (TBI) causes detrimental neurological conditions resulting from neuronal loss, damage to the blood-brain barrier (BBB), and secondary injury due to chronic neuroinflammation. Evidence shows that chronic tobacco use may exacerbate TBI neuropathology. The active component of tobacco, nicotine, activates neuronal nicotinic acetylcholine receptors (nAchRs). Caveolin-1 (Cav-1), a cholesterol-binding and scaffolding protein, localizes to plasmalemmal membrane lipid rafts (MLRs) and regulates nAchRs expression. Previous studies demonstrated that TBI alters MLRs and decreases Cav-1 and nAchR expression. However, it remains unknown if chronic nicotine exposure would aggravate TBI-induced neurobehavioral deficits. In this current study, we aim to elucidate the effects of chronic nicotine vaping and TBI on nAchRs expression and associated biochemical and behavioral changes. We used a murine controlled cortical impact (CCI) model to induce TBI. CCI mice were then subjected to vapor exposure for 6 weeks. Multiple behavioral tests were utilized to evaluate post-exposure changes in motor functions, social motivation, and object recognition memory. Immunoblot assays were used to assess nAchRs expression. Our findings demonstrated that chronic nicotine exposure inhibited social motivation in CCI mice. Recognition memory impairment was also observed due to TBI and chronic vaping. Biochemically, we observed decreased hippocampal β2-containing nAchRs in vapor-exposed Sham surgery and CCI mice; however, chronic nicotine alone did not alter Cav-1 expression. Overall, our findings suggest that the loss of β2-containing nAchRs due to chronic exposure to E-cigarette vapor may exacerbate CCI-induced behavioral deficits.