Abnormal expression of myelination genes and alterations in white matter fractional anisotropy following prenatal viral influenza infection at E16 in mice
Abnormal expression of myelination genes and alterations in white matter fractional anisotropy following prenatal viral influenza infection at E16 in mice
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DOI：
10.1016/j.schres.2009.04.014
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发表时间：
2009-07-01
影响因子：
4.5
通讯作者：
Oishi, Kenichi
中科院分区：
文献类型：
--
作者：
Fatemi, S. Hossein;Folsom, Timothy D.;Oishi, Kenichi
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，病毒感染会对小鼠后代的大脑结构和功能产生有害影响，这些小鼠后代在妊娠早期晚期（E9）和妊娠中期晚期（E18）接种流感病毒。我们假设，中孕中期感染（E16）小鼠可能会导致不同模式的大脑基因表达和结构缺陷的发展后代。在E16用亚致死剂量的人流感病毒感染C57 BL 6小鼠或使用载体溶液假感染。在P0、P14、P35和P56收集感染小鼠的雄性后代，取出其大脑，解剖小脑并快速冷冻。通过微阵列、DTI和MRI扫描以及qRT-PCR、SDS-PAGE和Western印迹分析来检测基因表达和脑萎缩的差异。发现与髓鞘形成相关的几个基因的表达，包括Mbp、Mag和Plp 1，以及Mbp、Mag和DM 20的蛋白质水平发生改变。脑成像显示P14时小脑显著萎缩，PO时右侧内囊白色物质的各向异性分数降低，P14时胼胝体和P56时右侧小脑中脚的白色物质的各向异性分数增加。我们认为母体感染影响小鼠髓鞘形成基因。(C)2009爱思唯尔有限公司版权所有。
Prenatal viral infection has been associated with the 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) and late second trimester (E18) administration of influenza virus. We hypothesized that middle second trimester infection (E16) in mice may lead to a different pattern of brain gene expression and structural defects in the developing offspring. C57BL6 mice were infected on E16 with a sublethal dose of human influenza virus or sham-infected using vehicle solution. Male offspring of the infected mice were collected at P0, P14, P35, and P56, their brains removed and cerebella dissected and flash frozen. Microarray, DTI and MRI scanning, as well as qRT-PCR and SDS-PAGE and western blotting analyses were performed to detect differences in gene expression and brain atrophy. Expression of several genes associated with myelination, including Mbp, Mag, and Plp1 were found to be altered, as were protein levels of Mbp, Mag, and DM20. Brain imaging revealed significant atrophy in cerebellum at P14, reduced fractional anisotropy in white matter of the right internal capsule at PO, and increased fractional anisotropy in white matter in corpus callosum at P14 and right middle cerebellar peduncle at P56. We propose that maternal infection in mouse impacts myelination genes. (C) 2009 Elsevier B.V. All rights reserved.