Paterson David S, Darnall Ryan
Department of Pathology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Auton Neurosci. 2009 May 11;147(1-2):48-55. doi: 10.1016/j.autneu.2009.01.004. Epub 2009 Feb 12.
The serotonergic (5-HT) system in the human medulla oblongata is well-recognized to play an important role in the regulation of respiratory and autonomic function. In this study, using both immunocytochemistry (n=5) and tissue section autoradiography with the radioligand (125)I-1-(2,5-dimethoxy-4-iodo-phenyl)2-aminopropane (n=7), we examine the normative development and distribution of the 5-HT(2A) receptor in the human medulla during the last part of gestation and first postnatal year when dramatic changes are known to occur in respiratory and autonomic control, in part mediated by the 5-HT(2A) receptor. High 5-HT(2A) receptor binding was observed in the dorsal motor nucleus of the vagus (preganglionic parasympathetic output) and hypoglossal nucleus (airway patency); intermediate binding was present in the nucleus of the solitary tract (visceral sensory input), gigantocellularis, intermediate reticular zone, and paragigantocellularis lateralis. Negligible binding was present in the raphé obscurus and arcuate nucleus. The pattern of 5-HT(2A) immunoreactivity paralleled that of binding density. By 15 gestational weeks, the relative distribution of the 5-HT(2A) receptor was similar to that in infancy. In all nuclei sampled, 5-HT(2A) receptor binding increased with age, with significant increases in the hypoglossal nucleus (p=0.027), principal inferior olive (p=0.044), and medial accessory olive (0.038). Thus, 5-HT(2A) receptors are concentrated in regions involved in autonomic and respiratory control in the human infant medulla, and their developmental profile changes over the first year of life in the hypoglossal nucleus critical to airway patency and the inferior olivary complex essential to cerebellar function.
人类延髓中的5-羟色胺能(5-HT)系统在调节呼吸和自主神经功能方面发挥重要作用,这一点已得到广泛认可。在本研究中,我们采用免疫细胞化学法(n = 5)和使用放射性配体(125)I-1-(2,5-二甲氧基-4-碘苯基)2-氨基丙烷的组织切片放射自显影法(n = 7),研究妊娠后期和出生后第一年人类延髓中5-HT(2A)受体的正常发育和分布情况。已知在这一时期,呼吸和自主神经控制会发生显著变化,部分由5-HT(2A)受体介导。在迷走神经背运动核(节前副交感神经输出)和舌下神经核(气道通畅)中观察到高5-HT(2A)受体结合;在孤束核(内脏感觉输入)、巨细胞网状核、中间网状带和外侧旁巨细胞网状核中存在中等结合。在中缝隐核和弓状核中结合可忽略不计。5-HT(2A)免疫反应模式与结合密度模式相似。到妊娠15周时,5-HT(2A)受体的相对分布与婴儿期相似。在所有采样核中,5-HT(2A)受体结合随年龄增加,舌下神经核(p = 0.027)、主要下橄榄核(p = 0.044)和内侧副橄榄核(0.038)有显著增加。因此,5-HT(2A)受体集中在人类婴儿延髓中参与自主神经和呼吸控制的区域,并且它们的发育情况在出生后第一年中发生变化,在对气道通畅至关重要的舌下神经核以及对小脑功能至关重要的下橄榄复合体中表现明显。