Preliminary evidence for a modulation of fetal dopaminergic development by maternal immune activation during pregnancy
Preliminary evidence for a modulation of fetal dopaminergic development by maternal immune activation during pregnancy
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DOI：
10.1016/j.neuroscience.2008.04.031
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发表时间：
2008-06-23
期刊：
影响因子：
3.3
通讯作者：
Feldon, J.
中科院分区：
文献类型：
--
作者：
Meyer, U.;Engler, A.;Feldon, J.
怀孕期间的母体感染是后代患上严重脑部疾病的环境风险因素，包括精神分裂症和自闭症。然而，关于产前暴露于感染与以后生活中出现的大脑和行为功能障碍之间关联的神经发育机制，人们知之甚少。利用病毒模拟多核糖素-多核糖素二酸（Polyl:C）的产前免疫攻击小鼠模型，我们探索了怀孕期间母体免疫激活对胎儿多巴胺能系统发育的急性影响，多巴胺能系统是一种已知在精神分裂症和相关疾病中受影响的神经递质系统。我们发现，妊娠早期/中期母体免疫刺激增加了妊娠中期/晚期胎儿大脑中脑多巴胺神经元的数量。这种影响与几个已知参与多巴胺神经元发育的基因的胎儿表达变化相似，包括诱导信号sonic hedgehog （Shh）和成纤维细胞生长因子8 (Fgf8)，以及转录因子Nurr1和Pitx3。这些发现为妊娠期间母体免疫激活对胎儿多巴胺能发育的调节提供了初步的体内证据。因此，有必要进一步研究产前免疫刺激对神经发育的影响，以进一步验证多巴胺能异常发育是否可能是子宫内暴露于感染后出现的精神分裂症样脑和行为功能障碍的关键神经病理机制。(c) 2008 ibro。Elsevier Ltd.出版。版权所有。
Maternal infection during pregnancy is an environmental risk factor for the offspring to develop severe brain disorders, including schizophrenia and autism. However, only little is known about the neurodevelopmental mechanisms underlying the association between prenatal exposure to infection and the emergence of brain and behavioral dysfunctions in later life. Using a mouse model of prenatal immune challenge by the viral mimic polyriboinosinic-polyribocytidilic acid (Polyl:C), we explored the acute effects of maternal immune activation during pregnancy on the development of the fetal dopaminergic system, a neurotransmitter system known to be affected in schizophrenia and related disorders. We found that maternal immunological stimulation in early/middle pregnancy increased the number of mesencephalic dopamine neurons in the fetal brain at middle/late and late gestation. This effect was paralleled by changes in fetal expression of several genes known to be involved in dopamine neuron development, including the inductive signals sonic hedgehog (Shh) and fibroblast growth factor 8 (Fgf8), as well as transcription factors Nurr1 and Pitx3. These findings provide initial in vivo evidence for a modulation of fetal dopaminergic development by maternal immune activation during pregnancy. Additional investigations of the neurodevelopmental effects of prenatal immune challenge are thus clearly warranted in order to further validate whether abnormal dopaminergic development may be a critical neuropathological mechanism underlying the precipitation of schizophrenia-like brain and behavioral dysfunctions emerging after in utero exposure to infection. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.