Kinney H C, O'Donnell T J, Kriger P, White W F
Department of Pathology, Children's Hospital, Boston, Massachusetts 02115.
Neuroscience. 1993 Aug;55(4):1127-38. doi: 10.1016/0306-4522(93)90326-b.
Little is known about the developmental profile of nicotinic cholinergic receptors in the developing human brain, despite the potential importance of such information in understanding the pathogenesis of neurological abnormalities or increased risk for the sudden infant death syndrome in offspring exposed to nicotine in utero. In this study, we determined the distribution of [3H]nicotine binding in the developing human brainstem by quantitative tissue autoradiography. In midgestational fetuses, [3H]nicotine binding sites were heavily concentrated in tegmental nuclei related to cardiopulmonary integration, arousal, attention, rapid eye movement sleep, and somatic motor control. Over the last half of gestation, [3H]nicotine binding decreased 60-70% in the tegmental nuclei, with a significant difference in binding between midgestation and early infancy. In contrast, there was essentially no change in [3H]nicotine binding in the major cerebellar-relay nuclei (principal inferior olive and griseum pontis) between the same time-points. Tritium quenching by increasing lipid (myelin) content in tissue sections did not account for the decreases in [3H]nicotine binding in tegmental nuclei. Based upon the high levels of [3H]nicotine binding at midgestation, combined with experimental data demonstrating trophic properties for acetylcholine, we postulate that nAChRs a role in the development of the brainstem tegmentum during this period, and that once this role is fulfilled, nicotinic cholinergic binding decreases and remains low thereafter. Alternatively, nicotinic cholinergic receptors may be critical for other developmentally related functions and/or neurotransmission in the brainstem tegmentum at midgestation. The high levels of [3H]nicotine binding in the brainstem tegmentum at midgestation and its rapidly changing profile over late gestation further suggest that mid-to-late gestation is a developmental period during which this region is likely to be most vulnerable to the harmful effects of nicotine in maternal cigarette smoke. The baseline information provided in this study is potentially relevant towards understanding attention deficits and risk for the sudden infant death syndrome in offspring exposed to cigarette smoke in utero.
尽管这些信息对于理解神经异常的发病机制或子宫内接触尼古丁的后代患婴儿猝死综合征风险增加具有潜在重要性，但人们对发育中的人类大脑中烟碱型胆碱能受体的发育情况知之甚少。在本研究中，我们通过定量组织放射自显影法确定了发育中的人类脑干中[3H]尼古丁结合的分布。在妊娠中期胎儿中，[3H]尼古丁结合位点高度集中在与心肺整合、觉醒、注意力、快速眼动睡眠和躯体运动控制相关的被盖核中。在妊娠的最后半个阶段，被盖核中的[3H]尼古丁结合减少了60 - 70%，妊娠中期和婴儿早期之间的结合存在显著差异。相比之下，在相同时间点之间，主要小脑中继核（主要下橄榄核和脑桥灰质）中的[3H]尼古丁结合基本没有变化。组织切片中脂质（髓磷脂）含量增加导致的氚淬灭并不能解释被盖核中[3H]尼古丁结合的减少。基于妊娠中期[3H]尼古丁结合的高水平，结合证明乙酰胆碱具有营养特性的实验数据，我们推测在此期间烟碱型乙酰胆碱受体在脑干被盖的发育中起作用，并且一旦这个作用完成，烟碱型胆碱能结合就会减少并在此后保持低水平。或者，烟碱型胆碱能受体在妊娠中期可能对脑干被盖中其他与发育相关的功能和/或神经传递至关重要。妊娠中期脑干被盖中[3H]尼古丁结合的高水平及其在妊娠后期迅速变化的情况进一步表明，妊娠中期至后期是该区域可能最易受母体香烟烟雾中尼古丁有害影响的发育时期。本研究提供的基线信息可能与理解子宫内接触香烟烟雾的后代的注意力缺陷和婴儿猝死综合征风险相关。
