Effects of cigarette smoke exposure on nicotinic acetylcholine receptor subunits alpha7 and beta2 in the sudden infant death syndrome (SIDS) brainstem.

摘要

It is postulated that nicotine, as the main neurotoxic constituent of cigarette smoke, influences SIDS risk through effects on nicotinic acetylcholine receptors (nAChRs) in brainstem nuclei that control respiration and arousal. This study compared alpha7 and beta2 nAChR subunit expression in eight nuclei of the caudal and rostral medulla and seven nuclei of the pons between SIDS (n=46) and non-SIDS infants (n=14). Evaluation for associations with known SIDS risk factors included comparison according to whether infants had a history of exposure to cigarette smoke in the home, and stratification for sleep position and gender. Compared to non-SIDS infants, SIDS infants had significantly decreased alpha7 in the caudal nucleus of the solitary tract (cNTS), gracile and cuneate nuclei, with decreased beta2 in the cNTS and increased beta2 in the facial. When considering only the SIDS cohort: 1-cigarette smoke exposure was associated with increased alpha7 in the vestibular nucleus and increased beta2 in the rostral dorsal motor nucleus of the vagus, rNTS and Cuneate, 2-there was a gender interaction for alpha7 in the gracile and cuneate, and beta2 in the cNTS and rostral arcuate nucleus, and 3-there was no effect of sleep position on alpha7, but prone sleep was associated with decreased beta2 in three nuclei of the pons. In conclusion, SIDS infants demonstrate differences in expression of alpha7 and beta2 nAChRs within brainstem nuclei that control respiration and arousal, which is independent on prior history of cigarette smoke exposure, especially for the NTS, with additional differences for smoke exposure (beta2), gender (alpha7 and beta2) and sleep position (beta2) evident.