Fanous A M, Machaalani R, Waters K A
Department of Anatomy and Histology, University of Sydney, NSW 2006, Sydney, Australia.
Neuroscience. 2006 Oct 13;142(2):401-9. doi: 10.1016/j.neuroscience.2006.06.042. Epub 2006 Aug 4.
Prone sleeping and cigarette smoke exposure are two major risk factors for the sudden infant death syndrome (SIDS). Utilizing piglet models of early postnatal nicotine and/or intermittent hypercapnic-hypoxia (IHH) exposure, we tested the hypothesis that these exposures, separately or combined, increase N-methyl-D-aspartate (NMDA) receptor 1 (NR1) expression in the brainstem medulla. We also tested for gender-specific effects. Three piglet exposure groups were compared against 14 controls; 1, nicotine [n = 14], 2, IHH [n = 10], and 3, nicotine+IHH [n = 14], with equal gender proportions in each group. Non-radioactive in situ hybridization and immunohistochemistry were performed for NR1 mRNA and protein expression, respectively, and were quantified in seven nuclei of the brainstem medulla. NR1 mRNA was significantly increased in the gracile and inferior olivary nucleus (ION) after nicotine exposure, in five of seven nuclei after IHH exposure, and in three of seven nuclei after nicotine+IHH. The increased mRNA changes were accompanied by increased protein only in the ION after IHH and nicotine+IHH (P = 0.019, and P = 0.008 respectively). By gender, control females had greater NR1 mRNA than males in the dorsal motor nucleus of vagus (P = 0.05) and for protein in the ION (P = 0.02). This gender difference was maintained after nicotine exposure in the ION with additional gender differences observed including greater mRNA in the cuneate nucleus (P = 0.04) and nucleus of the spinal trigeminal tract (P = 0.03) of males compared with females. Overall, more changes occurred at the mRNA level than protein, and IHH exposure induced more changes than nicotine or nicotine+IHH exposures. Together, these findings suggest that hypercapnic-hypoxic exposures (modeling prone sleeping or sleep apnea) are more likely to induce NMDA receptor changes in the developing brainstem than nicotine exposure alone.
俯卧睡眠和接触香烟烟雾是婴儿猝死综合征（SIDS）的两个主要危险因素。利用新生仔猪尼古丁和/或间歇性高碳酸血症 - 低氧血症（IHH）暴露模型，我们检验了以下假设：这些暴露单独或联合作用会增加脑干延髓中N - 甲基 - D - 天冬氨酸（NMDA）受体1（NR1）的表达。我们还测试了性别特异性影响。将三个仔猪暴露组与14个对照组进行比较；1. 尼古丁组[n = 14]，2. IHH组[n = 10]，3. 尼古丁 + IHH组[n = 14]，每组性别比例相等。分别对NR1 mRNA和蛋白质表达进行非放射性原位杂交和免疫组织化学检测，并在脑干延髓的七个核中进行定量分析。尼古丁暴露后，薄束核和下橄榄核（ION）中NR1 mRNA显著增加；IHH暴露后，七个核中有五个核的NR1 mRNA增加；尼古丁 + IHH暴露后，七个核中有三个核的NR1 mRNA增加。IHH和尼古丁 + IHH暴露后，仅ION中增加的mRNA变化伴随着蛋白质增加（分别为P = 0.019和P = 0.008）。按性别分析，对照雌性在迷走神经背运动核中的NR1 mRNA高于雄性（P = 0.05），在ION中的蛋白质也高于雄性（P = 0.02）。尼古丁暴露后，ION中这种性别差异依然存在，还观察到其他性别差异，包括与雌性相比，雄性楔束核（P = 0.04）和脊髓三叉神经核（P = 0.03）中的mRNA更多。总体而言呀，mRNA水平的变化比蛋白质水平更多，并且IHH暴露诱导的变化比尼古丁或尼古丁 + IHH暴露更多。总之，这些发现表明，高碳酸血症 - 低氧血症暴露（模拟俯卧睡眠或睡眠呼吸暂停）比单独尼古丁暴露更有可能在发育中的脑干中诱导NMDA受体变化。
