Nicotine in E-Cigarette Aerosol Reduces GABA Neuron Migration via the α7 Nicotinic Acetylcholine Receptor

Abstract

Prenatal nicotine exposure is linked to adverse neurodevelopmental outcomes, yet e-cigarette use during pregnancy continues to rise due to aggressive marketing efforts and misconceptions of safety. We investigated the effect of prenatal e-cigarette aerosol exposure on the migration of GABA neurons, a developmental process critical for the establishment of cerebral cortical circuitry. Pregnant mice were exposed to nicotine-containing aerosol (e-cigarette), nicotine-free aerosol (e-liquid) or room air (control) daily beginning 2 weeks before conception and continuing until gestational day 14. E-cigarette, but not e-liquid, aerosol significantly reduced GABA neuron density in the dorsal cerebral wall at rostral forebrain level and within the marginal zone, reflecting region-specific vulnerabilities. In vitro explant cultures revealed that nicotine dose-dependently reduced neuronal migration, and this effect was mimicked by a selective 7 nicotinic acetylcholine receptor (nAChR) agonist. Blocking the 7 nAChR using a selective antagonist attenuated the effects of nicotine on neuronal migration. These findings reveal a previously unrecognized vulnerability of GABA neuron migration to e-cigarette aerosol and identify 7 nAChR activation as a mechanism for nicotine-induced impairment of GABA neuron migration. Moreover, the findings highlight the need for translational efforts to update clinical guidance and public policy regarding e-cigarette use during pregnancy.