Increasing evidence indicates that the central nervous system (CNS) is a target of air pollution. We previously reported that postnatal exposure of mice to concentrated ambient ultrafine particles (UFP; ≤100 nm) via the University of Rochester HUCAPS system during a critical developmental window of CNS development, equivalent to human 3rd trimester, produced male-predominant neuropathological and behavioral characteristics common to multiple neurodevelopmental disorders, including autism spectrum disorder (ASD), in humans. The current study sought to determine whether vulnerability to fine (≤2.5 μm) and UFP air pollution exposure extends to embryonic periods of brain development in mice, equivalent to human 1st and 2nd trimesters. Pregnant mice were exposed 6 h/day from gestational days (GDs) 0.5-16.5 using the New York University VACES system to concentrated ambient fine/ultrafine particles at an average concentration of 92.69 μg/m3 over the course of the exposure period. At postnatal days (PNDs) 11-15, neuropathological consequences were characterized. Gestational air pollution exposures produced ventriculomegaly, increased corpus callosum (CC) area and reduced hippocampal area in both sexes. Both sexes demonstrated CC hypermyelination and increased microglial activation and reduced total CC microglia number. Analyses of iron deposition as a critical component of myelination revealed increased iron deposition in the CC of exposed female offspring, but not in males. These findings demonstrate that vulnerability of the brain to air pollution extends to gestation and produces features of several neurodevelopmental disorders in both sexes. Further, they highlight the importance of the commonalities of components of particulate matter exposures as a source of neurotoxicity and common CNS alterations.

Electronic cigarettes (e-cigarettes), battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS) transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation) throughout gestation (3 h/day; 5 days/week) to aerosols produced from e-cigarettes either with nicotine (13–16 mg/mL) or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND) 4–6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq). Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology.

Tobacco use, primarily in the form of cigarettes, is the leading cause of preventable morbidity and mortality in the United States (U.S.). The adverse effects of tobacco use began to be recognized in the 1940’s and new hazards of active smoking and secondhand smoke (SHS) exposure from cigarettes continue to be identified to this day. This has led to a sustained and wide-ranging array of highly effective regulatory, public health, and clinical efforts that have been informed by extensive scientific data, resulting in marked decreases in the use of cigarettes. Unfortunately, the dramatic recent decline in cigarette use in the U.S., has been accompanied by an upsurge in adolescent and young adult use of new, non-cigarette tobacco and nicotine-delivery products, commonly referred to as alternative tobacco products (ATPs). Commonly used ATPs include hookah, cigars, smokeless tobacco, and electronic cigarettes. While there have been a number of review articles that focus on adult ATP use, the purpose of this review is to provide an overview of what is, and is not known about emerging ATP use among U.S. adolescents on a national scale; as well as to identify research gaps in knowledge, and discuss future health and policy needs for this growing public health concern. This paper is not meant to systemically review all published survey data, but to present clear depiction of selected ATP usage in youth populations using national survey data.

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Background We examined the association of non-cigarette tobacco use on chronic obstructive pulmonary disease (COPD) risk in the Population Assessment of Tobacco and Health (PATH) Study. Methods There were 13,752 participants ≥ 40 years with Wave 1 (W1) data for prevalence analyses, including 6945 adults without COPD for incidence analyses; W1–5 (2013–2019) data were analyzed. W1 tobacco use was modeled as 12 mutually-exclusive categories of past 30-day (P30D) single and polyuse, with two reference categories (current exclusive cigarette and never tobacco). Prevalence and incidence ratios of self-reported physician-diagnosed COPD were estimated using weighted multivariable Poisson regression. Results W1 mean (SE) age was 58.1(0.1) years; mean cigarette pack-years was similar for all categories involving cigarettes and exclusive use of e-cigarettes (all > 20), greater than exclusive cigar users (< 10); and COPD prevalence was 7.7%. Compared to P30D cigarette use, never tobacco, former tobacco, and cigar use were associated with lower COPD prevalence (RR = 0.33, (95% confidence interval—CI) [0.26, 0.42]; RR = 0.57, CI [0.47, 0.70]; RR = 0.46, CI [0.28, 0.76], respectively); compared to never tobacco use, all categories except cigar and smokeless tobacco use were associated with higher COPD prevalence (RR former = 1.72, CI [1.33, 2.23]; RR cigarette = 3.00, CI [2.37, 3.80]; RR e-cigarette = 2.22, CI [1.44, 3.42]; RR cigarette + e-cigarette = 3.10, CI [2.39, 4.02]; RR polycombusted = 3.37, CI [2.44, 4.65]; RR polycombusted plus noncombusted = 2.75, CI]1.99, 3.81]). COPD incidence from W2-5 was 5.8%. Never and former tobacco users had lower COPD risk compared to current cigarette smokers (RR = 0.52, CI [0.35, 0.77]; RR = 0.47, CI [0.32, 0.70], respectively). Compared to never use, cigarette, smokeless, cigarette plus e-cigarette, and polycombusted tobacco use were associated with higher COPD incidence (RR = 1.92, CI [1.29, 2.86]; RR = 2.08, CI [1.07, 4.03]; RR = 1.99, CI [1.29, 3.07]; RR = 2.59, CI [1.60, 4.21], respectively); exclusive use of e-cigarettes was not (RR = 1.36, CI [0.55, 3.39]). Conclusions E-cigarettes and all use categories involving cigarettes were associated with higher COPD prevalence compared to never use, reflecting, in part, the high burden of cigarette exposure in these groups. Cigarette—but not exclusive e-cigarette—use was also strongly associated with higher COPD incidence. Compared to cigarette use, only quitting tobacco was protective against COPD development.

Tobacco products influence striatal dopamine (DA) release primarily through the actions of nicotine, an agonist of nicotinic acetylcholine receptors (nAChR). Gutkha is a smokeless tobacco product that contains not only nicotine, but also the habit-forming areca nut and other plant-based constituents that contribute muscarinic acetylcholine receptor (mAChR) agonists and other cholinergic agents. Thus, the net influence of the cholinergic agents in gutkha on striatal DA release difficult to predict. This study investigated the influence of gutkha extract on evoked DA release in mouse striatal slices using fast-scan cyclic voltammetry. The potency of a given concentration of nicotine in the gutkha extract was found to be significantly lower than that of a comparable concentration of nicotine alone. Atropine, a mAChR antagonist, increased the potency of gutkha-associated nicotine; however, other experiments suggested that this was mediated in part by direct effects of atropine at nAChRs. Overall, these results suggest that the unique constituents of gutkha work together to oppose the influence of gutkha-associated nicotine on evoked striatal DA release.