Maternal administration of thalidomide or valproic acid causes abnormal serotonergic neurons in the offspring: implication for pathogenesis of autism
Maternal administration of thalidomide or valproic acid causes abnormal serotonergic neurons in the offspring: implication for pathogenesis of autism
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DOI：
10.1016/j.ijdevneu.2004.05.004
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发表时间：
2005-04-01
影响因子：
1.8
通讯作者：
Narita, M
中科院分区：
文献类型：
--
作者：
Miyazaki, K;Narita, N;Narita, M
胚胎暴露于沙利度胺（塔尔）或丙戊酸（VPA）神经管关闭前已被证明是一个有用的模型，人类自闭症大鼠。在这些大鼠中已经显示了在人类自闭症中经常观察到的多巴胺能系统的缺失。因此，我们研究了早期多巴胺能神经元的发育是否受到塔尔/VPA的干扰。当孕鼠暴露于塔尔或VPA的胚胎9天，一个戏剧性的转变中缝背核中的多巴胺能神经元的分布观察到出生后50天。这种改变被认为反映了多巴胺能神经元分化和迁移的异常。体外研究表明，VPA延迟ES细胞衍生的神经元祖细胞的多巴胺能神经元的成熟，而外源性添加Sonic hedgehog，一种与多巴胺能细胞命运有关的形态发生素，部分阻止了这种延迟。这些结果表明，早期多巴胺能神经元发育的中断可能参与自闭症的病因。(C)2004 ISDN。由爱思唯尔有限公司出版。保留所有权利。
Embryonic exposure to thalidomide (THAL) or valproic acid (VPA) before neural tube closure has been demonstrated as a useful model for human autism in rats. Abnormalities of the serotonergic system which are often observed in human autism have been shown in these rats. Thus, we examined whether early serotonergic neuronal development is perturbed by THAL/VPA. When pregnant rats were exposed to THAL or VPA on embryonic day 9, a dramatic shift of the distribution of serotonergic neurons in the dorsal raphe nucleus was observed on postnatal day 50. This alteration is thought to reflect abnormality of serotonergic neuronal differentiation and migration. In vitro studies revealed that VPA retards the maturation of serotonergic neuron from ES cell-derived neuronal progenitors, whereas exogenously added Sonic hedgehog, a morphogen that has been implicated in serotonergic cell fate, partially prevented this retardation. These results indicate that disruption of early serotonergic neuronal development might be involved in the etiology of autism. (C) 2004 ISDN. Published by Elsevier Ltd. All rights reserved.