The effects of nicotine on the alpha-7 and beta-2 nicotinic acetycholine receptor subunits in the developing piglet...

Exposure to cigarette smoke is a major risk factor for sudden infant death syndrome (SIDS). We tested the hypothesis that nicotine increases expression of the nicotinic acetylcholine receptor (nAChR) subunits alpha7 and beta2 in a piglet model. Piglets exposed to 2mg/kg/day nicotine for 14 days postnatally (n=14) were compared to non-exposed controls (n=14), (equal gender proportions). Immunohistochemistry was performed to identify and quantify changes in, alpha7 and beta2 nAChR subunits in 8 nuclei of the medulla at both the rostral and caudal levels. Compared to controls, nicotine exposed piglets had decreased alpha7 in the rostral dorsal motor nucleus of the vagus (rDMNV) (p=0.01), and increased beta2 in the caudal DMNV (cDMNV) (p=0.05), caudal nucleus of the spinal trigeminal tract (cNSTT) (p=0.03) and caudal nucleus of the solitary tract (cNTS) (p=0.04). Analysis by gender showed that in the control group, compared to males, females had higher beta2 in the caudal hypoglossal (cXII) (p<0.01) and caudal inferior olivary (p=0.04) nuclei, while in the nicotine group females had higher beta2 in the cDMNV (p=0.02). Compared to control males, nicotine exposed males had lower beta2 in the cXII (p<0.01). Overall, changes in alpha7 were specific to nicotine exposure with no gender differentiation. Changes in beta2 were more widespread but showed gender-specific effects. These findings provide evidence that early postnatal exposure to nicotine significantly affects nAChR subunit expressions in the developing brainstem.