The viral theory of schizophrenia revisited: abnormal placental gene expression and structural changes with lack of evidence for H1N1 viral presence in placentae of infected mice or brains of exposed offspring.
The viral theory of schizophrenia revisited: abnormal placental gene expression and structural changes with lack of evidence for H1N1 viral presence in placentae of infected mice or brains of exposed offspring.
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DOI：
10.1016/j.neuropharm.2011.01.011
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发表时间：
2012-03
影响因子：
4.7
通讯作者：
Patel, Divyen H.
中科院分区：
文献类型：
--
作者：
Fatemi, S. Hossein;Folsom, Timothy D.;Rooney, Robert J.;Mori, Susumu;Kornfield, Tess E.;Reutiman, Teri J.;Kneeland, Rachel E.;Liesch, Stephanie B.;Hua, Kegang;Hsu, John;Patel, Divyen H.
研究人员早就注意到，有过多的精神分裂症患者出生在1月和3月。据推测，这种冬季出生效应可能是由于维生素D缺乏等各种原因造成的，也可能是由于母亲在怀孕期间受到感染造成的。怀孕期间感染多种病毒，包括流感和风疹，已知会增加后代患精神分裂症的风险。使用流感病毒或PolyI:C（一种病毒模拟物）的动物模型已经能够复制精神分裂症的许多脑形态、遗传和行为缺陷。利用小鼠产前病毒感染模型，我们的实验室已经表明，病毒感染在胚胎9、16和18天导致暴露的后代大脑基因表达异常和大脑结构异常。本研究的目的是检测胚胎妊娠第7天病毒感染后胎盘、海马和前额叶皮层的基因表达和形态变化。用流感病毒A/WSN/33株（H1N1）感染妊娠小鼠或用载体液假感染妊娠小鼠。在E16时，收获胎盘并准备用于微阵列分析或光镜检查。我们观察到胎盘中有77个基因显著上调，93个基因显著下调。在E7感染后暴露子代的大脑中，前额叶皮层（P0处6个基因表达上调，24个基因表达下调；P56处5个基因表达上调，14个基因表达下调）和海马（P0处4个基因表达上调，6个基因表达下调；P56处6个基因表达上调，13个基因表达下调）的基因表达发生变化。QRT-PCR证实了与缺氧、炎症、精神分裂症和自闭症相关的一些基因的变化方向和幅度。受感染小鼠的胎盘表现出许多形态异常，包括血栓的存在和免疫细胞的增加。此外，我们在感染小鼠的胎盘和暴露后代的大脑中寻找H1N1病毒特异性基因M1/M2、NA和NS1的存在，但没有发现。我们的研究结果表明，产前病毒感染破坏了胎盘、海马体和前额皮质的结构和基因表达，这可能解释了在没有证据表明病毒rna存在于靶组织的情况下，暴露的后代的有害影响。
Researchers have long noted an excess of patients with schizophrenia were born during the months of January and March. This winter birth effect has been hypothesized to result either from various causes such as vitamin D deficiency, or from maternal infection during pregnancy. Infection with a number of viruses during pregnancy including influenza, and rubella are known to increase the risk of schizophrenia in the offspring. Animal models using influenza virus or PolyI:C, a viral mimic, have been able to replicate many of the brain morphological, genetic, and behavioral deficits of schizophrenia. Using a murine model of prenatal viral infection, our laboratory has shown that viral infection on embryonic days 9, 16, and 18 leads to abnormal expression of brain genes and brain structural abnormalities in the exposed offspring. The purpose of the current study was to examine gene expression and morphological changes in the placenta, hippocampus, and prefrontal cortex as a result of viral infection on embryonic day 7 of pregnancy. Pregnant mice were either infected with influenza virus [A/WSN/33 strain (H1N1)] or sham-infected with vehicle solution. At E16, placentas were harvested and prepared for either microarray analysis or for light microscopy. We observed significant, upregulation of 77 genes and significant downregulation of 93 genes in placentas. In brains of exposed offspring following E7 infection, there were changes in gene expression in prefrontal cortex (6 upregulated and 24 downregulated at P0; 5 upregulated and 14 downregulated at P56) and hippocampus (4 upregulated and 6 downregulated at P0; 6 upregulated and 13 downregulated at P56). QRT-PCR verified the direction and magnitude of change for a number of genes associated with hypoxia, inflammation, schizophrenia, and autism. Placentas from infected mice showed a number of morphological abnormalities including presence of thrombi and increased presence of immune cells. Additionally, we searched for presence of H1N1 viral-specific genes for M1/M2, NA, and NS1 in placentas of infected mice and brains of exposed offspring and found none. Our results demonstrate that prenatal viral infection disrupts structure and gene expression of the placenta, hippocampus, and prefrontal cortex potentially explaining deleterious effects in the exposed offspring without evidence for presence of viral RNAs in the target tissues.
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影响因子：
64.8
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
通讯作者：
Speck, Nancy A.
影响因子：
15.9
作者：
Benigni, F;Atsumi, T;Bucala, R
通讯作者：
Bucala, R
DOI：
10.1002/ajmg.b.30697
发表时间：
2008-10-05
影响因子：
2.8
作者：
Anitha, A.;Nakamura, Kazuhiko;Mori, Norio
通讯作者：
Mori, Norio
影响因子：
3.2
作者：
Aronsson, F;Lannebo, C;Karlsson, H
通讯作者：
Karlsson, H
影响因子：
4.5
作者：
Fatemi, S. Hossein;Folsom, Timothy D.;Oishi, Kenichi
通讯作者：
Oishi, Kenichi