Panigrahy A, Filiano J, Sleeper L A, Mandell F, Valdes-Dapena M, Krous H F, Rava L A, Foley E, White W F, Kinney H C
Department of Neurology, Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
J Neuropathol Exp Neurol. 2000 May;59(5):377-84. doi: 10.1093/jnen/59.5.377.
The sudden infant death syndrome (SIDS) is postulated to result from a failure of homeostatic responses to life-threatening challenges (e.g. asphyxia, hypercapnia) during sleep. The ventral medulla participates in sleep-related homeostatic responses, including chemoreception, arousal, airway reflex control, thermoregulation, respiratory drive, and blood pressure regulation, in part via serotonin and its receptors. The ventral medulla in humans contains the arcuate nucleus, in which we have shown isolated defects in muscarinic and kainate receptor binding in SIDS victims. We also have demonstrated that the arcuate nucleus is anatomically linked to the nucleus raphé obscurus, a medullary region with serotonergic neurons. We tested the hypothesis that serotonergic receptor binding is decreased in both the arcuate nucleus and nucleus raphé obscurus in SIDS victims. Using quantitative autoradiography, 3H-lysergic acid diethylamide (3H-LSD binding) to serotonergic receptors (5-HT1A-D and 5-HT2 subtypes) was measured blinded in 19 brainstem nuclei. Cases were classified as SIDS (n = 52), acute controls (infants who died suddenly and in whom a complete autopsy established a cause of death) (n = 15), or chronic cases with oxygenation disorders (n = 17). Serotonergic binding was significantly lowered in the SIDS victims compared with controls in the arcuate nucleus (SIDS, 6 +/- 1 fmol/mg tissue; acutes, 19 +/- 1; and chronics, 16 +/- 1; p = 0.0001) and n. raphé obscurus (SIDS, 28 +/- 3 fmol/mg tissue; acutes, 66 +/- 6; and chronics, 59 +/- 1; p = 0.0001). Binding, however, was also significantly lower (p < 0.05) in 4 other regions that are integral parts of the medullary raphé/serotonergic system, and/or are derived, like the arcuate nucleus and nucleus raphé obscurus, from the same embryonic anlage (rhombic lip). These data suggest that a larger neuronal network than the arcuate nucleus alone is involved in the pathogenesis of SIDS, that is, a network composed of inter-related serotonergic nuclei of the ventral medulla that are involved in homeostatic mechanisms, and/or are derived from a common embryonic anlage.
婴儿猝死综合征（SIDS）被推测是由于睡眠期间对危及生命的挑战（如窒息、高碳酸血症）的稳态反应失败所致。延髓腹侧部分参与与睡眠相关的稳态反应，包括化学感受、觉醒、气道反射控制、体温调节、呼吸驱动和血压调节，部分是通过血清素及其受体实现的。人类的延髓腹侧包含弓状核，我们已发现SIDS受害者的弓状核中毒蕈碱和 kainate 受体结合存在孤立缺陷。我们还证明，弓状核在解剖学上与中缝隐核相连，中缝隐核是一个含有血清素能神经元的髓质区域。我们检验了这样一个假设，即SIDS受害者的弓状核和中缝隐核中的血清素能受体结合均减少。使用定量放射自显影技术，对19个脑干核团中血清素能受体（5-HT1A - D和5-HT2亚型）的3H-麦角酸二乙酰胺（3H-LSD结合）进行了盲法测量。病例分为SIDS组（n = 52）、急性对照组（突然死亡且完整尸检确定了死因的婴儿）（n = 15）或患有氧合障碍的慢性病例组（n = 17）。与对照组相比，SIDS受害者的弓状核（SIDS组，6 ± 1 fmol/mg组织；急性对照组，19 ± 1；慢性病例组，16 ± 1；p = 0.0001）和中缝隐核（SIDS组，28 ± 3 fmol/mg组织；急性对照组，66 ± 6；慢性病例组，59 ± 1；p = 0.0001）中的血清素能结合显著降低。然而，在延髓中缝/血清素能系统的另外4个组成部分区域，以及/或者像弓状核和中缝隐核一样源自相同胚胎原基（菱唇）的区域，结合也显著降低（p < 0.05）。这些数据表明，参与SIDS发病机制的神经元网络比单独的弓状核更大，也就是说，是一个由延髓腹侧相互关联的血清素能核团组成的网络，这些核团参与稳态机制，和/或源自共同的胚胎原基。
