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E-Cigarette Exposure Alters Neuroinflammation Gene and Protein Expression in a Murine Model: Insights from Perinatally Exposed Offspring and Post-Birth Mothers

Awada, Christina; Saporito, Antonio F; Zelikoff, Judith T; Klein, Catherine B
The use of E-cigarettes, often considered a safer alternative to traditional smoking, has been associated with high rates of cellular toxicity, genetic alterations, and inflammation. Neuroinflammatory impacts of cigarette smoking during pregnancy have been associated with increased risks of adverse childhood health outcomes; however, it is still relatively unknown if the same propensity is conferred on offspring by maternal vaping during gestation. Results from our previous mouse inhalation studies suggest such a connection. In this earlier study, pregnant C57BL/6 mice were exposed daily to inhaled E-cig aerosols (i.e., propylene glycol and vegetable glycerin, [PG/VG]), with or without nicotine (16 mg/mL) by whole-body inhalation throughout gestation (3 h/d; 5 d/week; total ~3-week) and continuing postnatally from post-natal day (PND) 4-21. As neuroinflammation is involved in the dysregulation of glucose homeostasis and weight gain, this study aimed to explore genes associated with these pathways in 1-mo.-old offspring (equivalent in humans to 12-18 years of age). Results in the offspring demonstrated a significant increase in glucose metabolism protein levels in both treatment groups compared to filtered air controls. Gene expression analysis in the hypothalamus of 1 mo. old offspring exposed perinatally to E-cig aerosols, with and without nicotine, revealed significantly increased gene expression changes in multiple genes associated with neuroinflammation. In a second proof-of-principal parallel study employing the same experimental design, we shifted our focus to the hippocampus of the postpartum mothers. We targeted the mRNA levels of several neurotrophic factors (NTFs) indicative of neuroinflammation. While there were suggestive changes in mRNA expression in this study, levels failed to reach statistical significance. These studies highlight the need for ongoing research on E-cig-induced alterations in neuroinflammatory pathways.
PMID: 38540381
ISSN: 2073-4425
CID: 5645042

E-Cigarette Exposure During Fetal Development Alters Protein Transporters and Gene Expression Activity in Neural Pathways Associated With Obesity in Mice [Meeting Abstract]

Awada, C; Blum, J L; Klein, C B; Zelikoff, J T
Electronic cigarettes (E-cigs), battery-powered devices containing vegetable glycerin and propylene glycol (PG/VG) as humectants, along with nicotine and flavors, are the most commonly used nicotine product amongst adolescents and young adults. Despite the lack of safety data, pregnant cigarette smokers are also turning to e-cigs as a 'safer' smoking alternative. This study hypothesized that like cigarette smoking, maternal vaping during pregnancy increases the risk of childhood obesity in the offspring. Thus, C57BL/6 mice were exposed both prenatally (3h/d; 5d/wk for ~3-wk) and postnatally from PND 4-21 to e-cig aerosols (50:50 PG/VG) with and without nicotine (16 mg/mL) and alterations in transcriptional and inflammatory activity in hypothalamic metabolic pathways associated with obesity were investigated. At 1-mo-of-age, offspring from filtered air (FA) control and both treatment groups were sacrificed, the hypothalami collected and expression of transporters associated with obesity (i.e., Glucose 1,2,3,4, PPARgamma, and Leptin) analyzed by Western blot. Results here demonstrated a significant increase in glucose transporter 1-4 expression in both the PG/VG alone and PG/VG plus nicotine treatment groups compared to control levels. In addition, gene expression of PPARgamma, LepRb, MC4R, SLC2A1 were significantly increased (p<0.01) in these same 1-moold offspring compared to matched FA controls. Alternatively, no significant changes in AMPK and POMC expression was observed between and amongst treatment groups. These findings suggest that like traditional cigarettes, early life exposure to vaping aerosols (with and without nicotine) predispose the young offspring to obesity later in life via e-cig-induced alterations in the neural-obesity pathways
ISSN: 1098-2280
CID: 5365932


Chapter by: Klein, Catherine B.; Costa, Max
in: Handbook on the Toxicology of Metals by
[S.l.] : Elsevier Inc., 2021
pp. 615-637
ISBN: 9780128229460
CID: 5189482

Launching the "Projections" series in mutation research reviews with a special issue on next generation sequencing [Editorial]

Klein, Catherine B; Parsons, Barbara L
PMID: 34893159
ISSN: 1388-2139
CID: 5107812

ToxPoint: Using Multiomics to Bridge the Gap Between Electronic Cigarette Research and Disease Etiology

Avenbuan, Oyemwenosa N; Klein, Catherine B; Zelikoff, Judith T
PMID: 33259631
ISSN: 1096-0929
CID: 4734842

Passing of the pen: Editorship of Mutation Research - Reviews in Mutation Research [Editorial]

Parsons, Barbara L; Klein, Catherine B
PMID: 32192647
ISSN: 1873-135x
CID: 4353702

Formaldehyde, Epigenetics, and Alzheimer's Disease

Wang, Fei; Chen, Danqi; Wu, Peipei; Klein, Catherine; Jin, Chunyuan
Alzheimer's disease (AD) is the most common form of dementia. The accumulation of β-amyloid plaques and intracellular neurofibrillary tangles of hyperphosphorylated tau protein are two hallmarks of AD. The β-amyloid and tau proteins have been at the center of AD research and drug development for decades. However, most of the clinical trials targeting β-amyloid have failed. Whereas the safety and efficacy of most tau-targeting drugs have not yet been completely assessed, the first tau aggregation inhibitor, LMTX, failed in a late-stage trial, leading to further recognition of the complexities of AD and reconsideration of the amyloid hypothesis and perhaps the tau hypothesis as well. Multilevel complex interactions between genetic, epigenetic, and environmental factors contribute to the occurrence and progression of AD. Formaldehyde (FA) is a widespread environmental organic pollutant. It is also an endogenous metabolite in the human body. Recent studies suggest that elevation of FA in the body by endogenous and/or exogenous exposure may play important roles in AD development. We have demonstrated that FA reduces lysine acetylation of cytosolic histones, thereby compromising chromatin assembly and resulting in the loss of histone content in chromatin, a conserved feature of aging from yeast to humans. Aging is an important factor for AD progression. Therefore, FA-induced inhibition of chromatin assembly and the loss of histones may contribute to AD initiation and/or development. This review will briefly summarize current knowledge on mechanistic insights into AD, focusing on epigenetic alterations and the involvement of FA in AD development. The exploration of chemical exposures as contributing factors to AD may provide new insights into AD mechanisms and could identify potential novel therapeutic targets.
PMID: 30964647
ISSN: 1520-5010
CID: 3903242

Emerging confluences of epigenetics and DNA repair in cancer and disease [Editorial]

Klein, Catherine B
PMID: 31395354
ISSN: 1873-135x
CID: 4034442

EMGS-50 living history project [Meeting Abstract]

Van, Gijssel H E; Klein, C B
During the 2017 annual EMGS meeting awards ceremony, background information was shared about the person who served as the inspiration for one of these awards: Alexander Hollaender. Afterwards, people would tell us their stories about the founding of the EMGS and their personal memories of Alexander Hollaender. Some members who were involved with the founding of the EMGS, as well as members who interacted with Alexander Hollaender, are still active within EMGS. It is therefore important to collect and archive these stories, not only to archive the history of EMGS, but also to perpetuate the historical and continued excitement in the field. Therefore, the " EMGS 50 - Living History" project was created. The purpose of the project is to collect stories/memories from any member of the society. This project is modelled after the NPR StoryCorps' project, such that video stories will be collected for the EMGS history project. These stories will be published, with other relevant documents, on a timeline on the EMGS website, to create an interactive " living" history document of the EMGS. The goal of the project is to create at least one video for every year since EMGS began. This project is financially supported by the EMGS Endowment Fund and approved by the EMGS executive board. Inaugural videos will be collected during the 2018 the annual meeting and will serve as the basis for the 50th Anniversary symposium at the 50th Annual Meeting in Washington DC in 2019. Please join us in the video recording area and share your memories with EMGS. Instructions will be provided
ISSN: 1098-2280
CID: 3331222

Microglia Activation and Gene Expression Alteration of Neurotrophins in the Hippocampus Following Early Life Exposure to E-cigarette Aerosols in a Murine Model

Zelikoff, Judith T; Parmalee, Nancy; Corbett, Kevin; Gordon, Terry; Klein, Catherine B; Aschner, Michael
Recent epidemiological data indicate that the popularity of electronic cigarettes (e-cigarettes), and consequently nicotine use, is rising in both adolescent and adult populations. As nicotine is a known developmental neurotoxin, these products present a potential threat for those exposed during early life stages. Despite this, few studies have evaluated the toxicity of e-cigarettes on the developing central nervous system (CNS). The goal of this study was to assess neurotoxicity resulting from early life exposure to electronic cigarette aerosols in an in vivo model. Specifically, studies here focused on neuro-parameters related to neuroinflammation and neurotrophins. To accomplish this, pregnant and neonatal C57BL/6 mice were exposed to aerosols produced from classic tobacco flavor e-cigarette cartridges (with [13 mg/ml] and without nicotine) during gestation ( approximately 3-wk) and lactation ( approximately 3-wk) via whole-body inhalation. Exposure to e-cigarette aerosols with and without nicotine caused significant reductions in hippocampal gene expression of Ngfr and Bdnf, as well as in serum levels of cytokines IL-1beta, IL-2 and IL-6. Exposure to e-cigarette aerosols without nicotine enhanced expression of Iba-1, a specific marker of microglia, in the CA1 region of the hippocampus. Overall, our novel results indicate that exposure to e-cigarette aerosols, with and without nicotine, poses a considerable risk to the developing CNS. Consequently, e-cigarettes should be considered a potential public health threat, especially early in life, requiring further research and policy considerations.
PMID: 29161446
ISSN: 1096-0929
CID: 2792372