Say Meichien, Machaalani Rita, Waters Karen A
Department of Paediatrics and Child Health, University of Sydney, NSW 2006, Australia.
Brain Res. 2007 Jun 4;1152:17-26. doi: 10.1016/j.brainres.2007.03.037. Epub 2007 Mar 19.
We studied the effects of intermittent hypercapnic hypoxia (IHH) and/or nicotine on the immunoreactivity of serotoninergic (5-HT) receptors 1A and 2A in the piglet brainstem. These exposures were developed to mimic two common risk factors for Sudden Infant Death Syndrome (SIDS); prone sleeping (IHH) and cigarette smoke exposure (nicotine). Immunoreactivity for 5-HT(1A)R and 5-HT(2A)R were studied in four nuclei of the caudal medulla. Three exposure groups were compared to controls (n=14): IHH (n=10), nicotine (n=14), and nicotine+IHH (n=14). In control piglets, the immunoreactivity of 5-HT(1A)R was highest in the hypoglossal nucleus (XII), followed by inferior olivary nucleus (ION), nucleus of the solitary tract (NTS) and dorsal motor nucleus of the vagus (DMNV), whereas for 5-HT(2A)R, the immunoreactivity was highest in DMNV/NTS and then ION. Compared to controls, IHH reduced 5-HT(1A)R immunoreactivity in all studied nuclei (p<0.05) but had no effect on 5-HT(2A)R immunoreactivity. Nicotine reduced 5-HT(1A)R immunoreactivity in the DMNV, ION and NTS (p<0.001), and reduced 5-HT(2A)R immunoreactivity in DMNV/NTS (p<0.05). Nicotine+IHH reduced 5-HT(1A)R in DMNV, ION and NTS (p<0.001) but had no effect on 5-HT(2A)R immunoreactivity. Effects of nicotine on the DMNV were more significant in males compared to the females. These results show for the first time that IHH and/or nicotine can reduce 5-HT receptor immunoreactivity within functionally important nuclei of the piglet medulla. The findings support our hypothesis that 5-HT receptor abnormalities may be caused by postnatal exposures to clinically-relevant stimuli such as cigarette smoke exposure and/or prone sleeping.
我们研究了间歇性高碳酸血症性缺氧（IHH）和/或尼古丁对仔猪脑干中5-羟色胺能（5-HT）受体1A和2A免疫反应性的影响。这些暴露条件旨在模拟婴儿猝死综合征（SIDS）的两个常见风险因素；俯卧睡眠（IHH）和接触香烟烟雾（尼古丁）。我们研究了延髓尾部四个核团中5-HT（1A）R和5-HT（2A）R的免疫反应性。将三个暴露组与对照组（n = 14）进行比较：IHH组（n = 10）、尼古丁组（n = 14）和尼古丁+IHH组（n = 14）。在对照仔猪中，5-HT（1A）R的免疫反应性在舌下神经核（XII）中最高，其次是下橄榄核（ION）、孤束核（NTS）和迷走神经背运动核（DMNV），而对于5-HT（2A）R，免疫反应性在DMNV/NTS中最高，然后是ION。与对照组相比，IHH降低了所有研究核团中5-HT（1A）R的免疫反应性（p<0.05），但对5-HT（2A）R的免疫反应性没有影响。尼古丁降低了DMNV、ION和NTS中5-HT（1A）R的免疫反应性（p<0.001），并降低了DMNV/NTS中5-HT（2A）R的免疫反应性（p<0.05）。尼古丁+IHH降低了DMNV、ION和NTS中5-HT（1A）R的表达（p<0.001），但对5-HT（2A）R的免疫反应性没有影响。与雌性相比，尼古丁对雄性DMNV的影响更显著。这些结果首次表明，IHH和/或尼古丁可降低仔猪延髓功能重要核团内5-HT受体的免疫反应性。这些发现支持了我们的假设，即5-HT受体异常可能是由于出生后接触临床相关刺激，如接触香烟烟雾和/或俯卧睡眠所致。
