Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: Implications for genesis of neurodevelopmental disorders
Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: Implications for genesis of neurodevelopmental disorders
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DOI：
10.1016/j.schres.2007.11.018
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发表时间：
2008-02-01
影响因子：
4.5
通讯作者：
Juckel, Georg
中科院分区：
文献类型：
--
作者：
Fatemi, S. Hossein;Reutiman, Teri J.;Juckel, Georg
产前病毒感染与精神分裂症和自闭症的发展有关。我们的实验室先前已经表明，病毒感染会对妊娠早期晚期（E9）给予流感病毒后的小鼠后代的脑结构和功能产生有害影响。我们假设，小鼠妊娠中期感染（E18）可能导致发育中的后代出现不同的脑基因表达模式和结构缺陷。C57 BL 6 J小鼠在E18感染亚致死剂量的人流感病毒或使用载体溶液进行假感染。在P0、P14、P35和P56收集感染小鼠的雄性后代，取出它们的脑，解剖前额叶皮质、海马和小脑并快速冷冻。通过基因芯片、qRT-PCR、DTI和MRI扫描、蛋白质印迹和神经化学分析来检测基因表达的差异和脑萎缩。发现与精神分裂症或自闭症相关的几个基因（包括Sema 3a、Trfr 2和Vld 1 r）的表达发生了改变，Foxp 2的蛋白水平也发生了改变。用亚致死剂量的人流感病毒感染C57 BL 6 J小鼠，导致发育中小鼠后代的额叶、海马和小脑皮质发生了显著的基因改变。脑成像显示几个脑区明显萎缩，胼胝体白色物质变薄。最后，神经化学分析显示5-羟色胺（P14，P35），5-羟基吲哚乙酸（P14）和牛磺酸（P35）水平显著改变。我们建议，母体感染小鼠提供了一个启发式的动物模型，研究环境的贡献，精神分裂症和自闭症的发生，神经发育障碍的两个重要例子。(C)2008 Elsevier B. V.保留所有权利。
Prenatal viral infection has been associated with development of schizophrenia and autism. Our laboratory has previously shown that viral infection causes deleterious effects on brain structure and function in mouse offspring following late first trimester (E9) administration of influenza virus. We hypothesized that late second trimester infection (E 18) in mice may lead to a different pattern of brain gene expression and structural defects in the developing offspring.C57BL6J mice were infected on E 18 with a sublethal dose of human influenza virus or sham-infected using vehicle solution. Male offsping of the infected mice were collected at P0, P14, P35 and P56, their brains removed and prefrontal cortex, hippocampus and cerebellum dissected and flash frozen. Microarray, qRT-PCR, DTI and MRI scanning, western blotting and neurochemical analysis were performed to detect differences in gene expression and brain atrophy. Expression of several genes associated with schizophrenia or autism including Sema3a, Trfr2 and Vld1r were found to be altered as were protein levels of Foxp2.E18 infection of C57BL6J mice with a sublethal dose of human influenza virus led to significant gene alterations in frontal, hippocampal and cerebellar cortices of developing mouse progeny. Brain imaging revealed significant atrophy in several brain areas and white matter thinning in corpus callosum. Finally, neurochemical analysis revealed significantly altered levels of serotonin (P14, P35), 5-Hydroxyindoleacetic acid (P14) and taurine (P35). We propose that maternal infection in mouse provides an heuristic animal model for studying the environmental contributions to genesis of schizophrenia and autism, two important examples of neurodevelopmental disorders. (C) 2008 Elsevier B.V. All rights reserved.