Effects of chronic prenatal nicotine exposure on gene expression in neurotransmitter systems of the rat carotid body chemoafferent pathway

Abstract

Maternal smoking during pregnancy is a major risk factor for sudden infant death syndrome (SIDS) and nicotine is the key component implicated. Impaired ventilatory and arousal responses to low PO2 (hypoxia) during sleep are hallmarks of SIDS that have been observed in infants of smoking mothers and linked to prenatal nicotine exposure in animal models. Low PO2 stimulates the carotid body (CB), which receives afferent innervation from the petrosal ganglion (PG), initiating a chemoreflex that increases ventilation and can provoke wakefulness. Using a rat model, the objective of this study was to determine the effects of chronic prenatal nicotine exposure (1 mg / kg body weight / day) on gene expression within the cholinergic and dopaminergic neurotransmitter systems involved in the regulation of this reflex. After chronic nicotine, QPCR data revealed the upregulation of a2, a3, a6, b2, b3, and b4 nicotinic acetylcholine receptor (nAChR) subunits in the CB (a4, a5, a7, a9 unchanged, a10 downregulated) versus the downregulation of a2, a3, a4, a7, a9, a10, b2, b3 and b4 nAChR subunits in the PG (a5 absent, a6 unchanged). In the CB, tyrosine hydroxylase (TH) was upregulated and the dopamine transporter (DAT) was unchanged. In the PG, TH was upregulated and the DAT was downregulated. Future studies will determine whether changes in nAChR function correlate with observed changes in subunit expression. Supported by CIHR and NSERC.