Authors :
Presenting Author: Silvia Santana, ScD – University of Alabama at Birmingham
Michael Taylor, PhD – Virginia Tech
Laura B. Murdaugh, PhD – Virginia Tech
Xi Guo, PhD – University of Alabama at Birmingh
Matthew W. Buczynski, PhD – Virginia Tech
Ann M. Gregus, PhD – Virginia Tech
Susan Campbell, PhD – University of Alabama at Birmingham
Rationale:
Sickle cell disease (SCD) is a recessive inherited disorder caused by a point mutation in the hemoglobin chain of red blood cells, which cause significant morbidity and poor quality of life due to chronic pain. In the United States, more than 100,000 people are affected by SCD, mostly from minority ethnicities, with an annual cost of over $1.1 billion. Seizures are a common complication for people with SCD, who are 2-3 times more prone to having seizures. Conventional smoking can exacerbate the risk of SCD-related complications, including seizures and vaso-occlusive crisis[1].
Electronic nicotine delivery systems (ENDS), or electronic cigarettes, are complex electronic devices that heat a liquid to create an aerosol containing solvents and nicotine, which is inhaled or vaped by individuals (vaping). While conventional smoking is deadly, vaping was initially advertised as less harmful. However, recent data questions the effect of vaping on central nervous system function and highlight the urgent need for studies to elucidate the adverse health effects of electronic cigarettes in SCD, a disorder that is highly susceptible to seizures[2]. Furthermore, data from human studies and rodent epilepsy models show that alteration the gut microbiome is associated with seizures [3]. Although nicotine exposure can disrupt the composition of the gut microbiome, it is unknown if vaping nicotine alters the gut microbiome in SCD to impact seizure susceptibility. Together, the effects of nicotine vapor exposure on gut microbiome composition and seizure susceptibility in the context of SCD has not been studied, which is the focus of this study.
Methods: Townes mice expressing either normal adult human hemoglobin
(HbAA) or SCD (HbSS) were exposed to room air or nicotine vapor, 8 hours per day for 10 weeks. Fecal samples were collected before and 10 weeks after nicotine exposure and 16s rRNA sequencing was performed to assess changes in gut microbiota. Mice were administered pentylenetetrazole (PTZ) to induce and assess seizure susceptibility. All experimental procedures involving animals were performed following the NIH guidelines for animal care and use.
Results: Nicotine vapor exposure modulated the composition of the gut microbiome in HbAA and HbSS mice. Furthermore, nicotine exposure via electronic cigarettes significantly decreased seizure latency to PTZ-induced seizure.
Conclusions: Our data underscore the detrimental impact of nicotine exposure via ENDS device on central nervous system and peripheral function; revealing new observation that exposure to nicotine using ENDS device increases seizure susceptibility in the context of SCD.
Funding: NIH NINDS 1R21NS131301