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

Toxicol Sci. 2018 Mar 1;162(1):276-286. doi: 10.1093/toxsci/kfx257.

Abstract

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. 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 (∼3 weeks) and lactation (∼3 weeks) 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-1β, IL-2, and IL-6. Exposure to e-cigarette aerosols without nicotine enhanced expression of Iba-1, a specific marker of microglia, in the cornus ammonis 1 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 central nervous system. Consequently, e-cigarettes should be considered a potential public health threat, especially early in life, requiring further research and policy considerations.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Inhalation
  • Aerosols / toxicity*
  • Animals
  • Animals, Newborn
  • Cytokines / blood
  • Electronic Nicotine Delivery Systems*
  • Female
  • Gene Expression Profiling
  • Hippocampus / drug effects*
  • Hippocampus / growth & development
  • Hippocampus / metabolism
  • Mice, Inbred C57BL
  • Microglia / drug effects*
  • Microglia / immunology
  • Microglia / metabolism
  • Nerve Growth Factors / genetics*
  • Nicotine / toxicity
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / metabolism
  • Transcriptome / drug effects*

Substances

  • Aerosols
  • Cytokines
  • Nerve Growth Factors
  • Nicotine