Pennington S N, Sandstrom L P, Shibley I A, Long S D, Beeker K R, Smith C P, Lee K, Jones T A, Cummings K M, Means L W
Department of Biochemistry, School of Medicine, Greenville, NC 27858.
Brain Res Dev Brain Res. 1994 Dec 16;83(2):181-9. doi: 10.1016/0165-3806(94)00135-9.
Fetal growth suppression associated with chronic maternal intake of cigarette smoke is frequently observed in humans and studies using animal models suggest that in utero nicotine exposure is an important component of this growth suppression. The developing fetal central nervous system (CNS) is sensitive to the growth inhibitory effect of nicotine and morphological as well as functional CNS deficits may result from fetal nicotine exposure. The studies presented here show that nicotine exposure during early embryonic development ultimately inhibits the ability of 7-11 day old chicks to learn a detour task. The brain growth suppression caused by nicotine is paralleled by a failure of the early embryo brain to express the normal developmental increase in ornithine decarboxylase (ODC) activity. This biochemical change may be germane to the mechanism of nicotine-induced growth inhibition and/or nicotine-induced behavioral changes because the appropriate expression of ODC activity is essential to normal growth and differentiation in the fetal CNS. In the chick embryo, nicotine exposure alters several important signaling pathways that regulate ODC expression. For example, nicotine exposure lowers embryonic brain glucose levels and causes significant decreases in whole brain cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels and in cyclic AMP binding proteins (protein kinase-A regulatory activity). Also, in cultured chick cells, nicotine inhibits the ability of a potent mitogen (insulin) to induce ODC activity, but, paradoxically, in ovo nicotine exposure increased insulin binding and stimulated insulin receptor autophosphorylation in brain membranes.
人类中经常观察到与母亲长期吸入香烟烟雾相关的胎儿生长抑制，并且使用动物模型的研究表明，子宫内尼古丁暴露是这种生长抑制的一个重要因素。发育中的胎儿中枢神经系统（CNS）对尼古丁的生长抑制作用敏感，胎儿尼古丁暴露可能导致中枢神经系统的形态和功能缺陷。本文所呈现的研究表明，早期胚胎发育期间的尼古丁暴露最终会抑制7至11日龄雏鸡学习迂回任务的能力。尼古丁引起的脑生长抑制与早期胚胎脑未能表达鸟氨酸脱羧酶（ODC）活性的正常发育性增加并行。这种生化变化可能与尼古丁诱导的生长抑制机制和/或尼古丁诱导的行为变化密切相关，因为ODC活性的适当表达对于胎儿中枢神经系统的正常生长和分化至关重要。在鸡胚中，尼古丁暴露会改变几种调节ODC表达的重要信号通路。例如，尼古丁暴露会降低胚胎脑葡萄糖水平，并导致全脑环磷酸腺苷（环AMP）水平和环AMP结合蛋白（蛋白激酶 - A调节活性）显著降低。此外，在培养的鸡细胞中，尼古丁会抑制一种强效促有丝分裂原（胰岛素）诱导ODC活性的能力，但矛盾的是，在鸡胚中尼古丁暴露会增加胰岛素结合并刺激脑膜中的胰岛素受体自磷酸化。
