Neuroinflammatory and Behavioral Outcomes Measured in Adult Offspring of Mice Exposed Prenatally to E-Cigarette Aerosols

Abstract

BACKGROUND: In an effort to decrease the rates of smoking conventional tobacco cigarettes, electronic cigarettes (e-cigarettes) have been proposed as an effective smoking cessation tool. However, little is known about their toxicological impacts. This is concerning given that e-cigarette use is perceived as less harmful than conventional tobacco cigarettes during pregnancy for both the mother and fetus. OBJECTIVE: The goal of this study was to test the neurodevelopmental consequences of maternal e-cigarette use on adult offspring behavior and neuroimmune outcomes. METHODS: Pregnant female CD-1 mice were randomly assigned to one of three treatment groups (n = 8-10 per group) and exposed daily to either filtered air, propylene glycol and vegetable glycerol (50:50 PG/VG vehicle), or to PG/VG with 16 mg=mL nicotine (+Nic). Whole-body exposures were carried out for 3 h/d, 7 d/week, from gestational day (GD)0.5 until GD17.5. Adult male and female offspring (8 weeks old) were assessed across a battery of behavioral assessments followed by region-specific quantification of brain cytokines using multiplex immunoassays. RESULTS: Adult offspring of both sexes exposed to +Nic exhibited elevated locomotor activity in the elevated plus maze and altered stress-coping strategies in the forced swim task. Moreover, male and female offspring exposed to PG/VG with and without nicotine had a 5.2% lower object discrimination score in the novel object recognition task. In addition to differences in offspring behavior, maternal e-cigarette exposure with nicotine led to a reduction in interleukin (IL)-4 and interferon-gamma (IFNc) in the diencephalon, as well as lower levels of hippocampal IFNc (females only). Ecigarette exposure without nicotine resulted in a 2-fold increase of IL-6 in the cerebellum. DISCUSSION: These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy.

The fog, the attractive and the addictive: pulmonary effects of vaping with a focus on the contribution of each major vaping liquid constituent

“…Propylene glycol or glycerol exposure does not induce body weight changes in male or female mice [23,24]. Interestingly, neonatal exposure to propylene glycol and/or glycerol can decrease weight gain in offspring [25,26].…”

“…Nicotine vapours also decrease grip strength and swimming abilities in mice [69]. Adult mice exposed in utero to nicotine show behavioural changes as well, with either increased locomotor activity [24] or increased cognitive flexibility when subjected to the water maze test [26].…”

“…Animal studies Physiology Some reports show that exposure to nicotine vapours does not affect weight gain in male [24,67] or female mice [23,24]. Others show weight loss in adult male mice [23,64,68] and in adult males exposed to nicotine vapours at the neonatal stage [25,26].…”

Effects of E-Cigarette Exposure on Prenatal Life and Childhood Respiratory Health: A Review of Current Evidence

“…With regard to neurodevelopmental consequences of maternal EC use, adverse behavioral outcomes have been observed in mice adult offspring. Even without nicotine, being exposed daily to PG/VG all through the gestation period may disrupt learning and memory performance and cause a rise in neuro-inflammation (14). Previously, Nguyen et al identified changes in the behavior of the offspring of mice exposed to EC vapor with and without nicotine during pregnancy: mice showed a higher rate of shortterm memory deficits, learning disabilities, and increased anxious behavior, were more hyperactive and tended to explore the environment in risky ways compared to non-exposed ones.…”

E-Cigarette Aerosols and the Brain: Behavioral and Neuroinflammatory Changes in Prenatally Exposed Adult Mice

“… 3 Many users perceive e-cigarettes as a safer alternative to combustible cigarettes during pregnancy, 4 and in surveys published between 2007 and 2017, up to 15% of pregnant women in the United States reported using e-cigarettes. 4 , 5 However, a recent study in Environmental Health Perspectives 6 adds to the evidence that e-cigarettes are not risk free.…”