Nicotine influence on cerebrovascular and neurocognitive function with in utero electronic cigarette exposure
Abstract
Emerging studies find arteriolar dysfunction in offspring with in utero electronic-cigarette (Ecig) exposure, but the long-term effects on offspring's cerebrovascular and neurocognitive health are poorly understood. Ecigs provides a unique opportunity to directly evaluate the contributions of inhaled nicotine from the vehicle e-liquid, which was not possible with cigarettes. Moreover, many Ecigs have variable power settings, which can alter aerosol toxicity. We hypothesize that maternal vaping at different wattages will have variable effects on offspring cerebrovascular function and would be independent of nicotine. We used time-mated female Sprague-Dawley rats with Ecig exposure from gestation day (GD)2 to 21. We studied male and female offspring at 1, 3, 6 and 12 months of age, and found the magnitude of middle cerebral artery (MCA) impairment in offspring was greater at 30 W vs. 5 W, but that both conditions significantly impaired MCA function. Vascular dysfunction was evident with or without nicotine in the e-liquid, but nicotine exposure (50 mg/ml e-liquid) resulted in short-term memory deficits, evidence of neuronal damage, and increased astrocyte interaction with endothelial cells in 6- and 12-month-old offspring. We also observed altered expression of clock genes and antioxidant signalling pathways, along with a decrease in sirtuin-1 expression, a decreased ratio of beta-amyloid (Aβ) 42/40 protein expression, and an increase in NADPH oxidase 1, which are consistent…
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