Maternal immune activation alters behavior in adult offspring, with subtle changes in the cortical transcriptome and epigenome.
Maternal immune activation alters behavior in adult offspring, with subtle changes in the cortical transcriptome and epigenome.
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DOI：
10.1016/j.schres.2012.06.037
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发表时间：
2012-09
影响因子：
4.5
通讯作者：
Akbarian S
中科院分区：
文献类型：
--
作者：
Connor CM;Dincer A;Straubhaar J;Galler JR;Houston IB;Akbarian S
产前发育期间的母体免疫激活，包括用病毒RNA模拟物、多聚核糖肌苷酸-多聚核糖胞苷酸（poly IC）的治疗，用作广泛使用的动物模型以诱导使人联想到精神分裂症和相关疾病的行为缺陷。在这里，我们报告说，大规模的细胞因子激活后，单剂量的聚IC在产前期间与持久的工作记忆缺陷的成年后代。为了探讨大脑皮层中基因表达失调是否会导致认知功能障碍，我们分析了皮层转录组，此外，绘制了三甲基化组蛋白H3-赖氨酸4（H3 K4 me 3）的全基因组分布，这是一种在转录单位5′端受到强烈调控的表观遗传标记。然而，深测序为基础的H3 K4 me 3映射和基因芯片分析并没有发现显着的变化后，在胚胎天E17.5或E12.5聚IC暴露在成熟的大脑皮层。在一个小的位点，H3 K4 me 3是敏感的激活细胞因子信号在原代培养的胎儿前脑，但成年皮质的生理盐水和聚IC暴露的小鼠没有表现出显着的差异。转录起始位点（TSS）的一个小的子集，包括分裂症1（Disc 1），一个精神分裂症的风险基因往往涉及基因-环境相互作用模型，显示改变H3 K4 me 3产前多聚IC后，但这些差异都没有生存后校正多重比较。我们的结论是，产前多聚IC与认知缺陷以后的生活，但没有强大的改变大脑皮层中的基因表达的表观遗传调控。
Maternal immune activation during prenatal development, including treatment with the viral RNA mimic, polyriboinosinic-polyribocytidilic acid (poly IC), serves as a widely used animal model to induce behavioral deficits reminiscent of schizophrenia and related disease. Here, we report that massive cytokine activation after a single dose of poly IC in the prenatal period is associated with lasting working memory deficits in adult offspring. To explore whether dysregulated gene expression in cerebral cortex, contributes to cognitive dysfunction, we profiled the cortical transcriptome, and in addition, mapped the genome-wide distribution of trimethylated histone H3-lysine 4 (H3K4me3), an epigenetic mark sharply regulated at the 5′end of transcriptional units. However, deep sequencing-based H3K4me3 mapping and and mRNA profiling by microarray did not reveal significant alterations in mature cerebral cortex after poly IC exposure at embryonic days E17.5 or E12.5. At a small set of loci, H3K4me3 was sensitive to activation of cytokine signaling in primary cultures from fetal forebrain but adult cortex of saline- and poly IC-exposed mice did not show significant differences. A small subset of transcription start sites (TSS), including Disrupted-in-Schizophrenia 1 (Disc1), a schizophrenia risk gene often implicated in gene-environment interaction models, showed altered H3K4me3 after prenatal poly IC but none of these differences survived after correcting for multiple comparisons. We conclude that prenatal poly IC is associated with cognitive deficits later in life, but without robust alterations in epigenetic regulation of gene expression in the cerebral cortex.
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影响因子：
16
作者：
Kanhere A;Viiri K;Araújo CC;Rasaiyaah J;Bouwman RD;Whyte WA;Pereira CF;Brookes E;Walker K;Bell GW;Pombo A;Fisher AG;Young RA;Jenner RG
通讯作者：
Jenner RG
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
10.6
作者：
Abazyan, Bagrat;Nomura, Jun;Kannan, Geetha;Ishizuka, Koko;Tamashiro, Kellie L.;Nucifora, Frederick;Pogorelov, Vladimir;Ladenheim, Bruce;Yang, Chunxia;Krasnova, Irina N.;Cadet, Jean Lud;Pardo, Carlos;Mori, Susumu;Kamiya, Atsushi;Vogel, Michael W.;Sawa, Akira;Ross, Christopher A.;Pletnikov, Mikhail V.
通讯作者：
Pletnikov, Mikhail V.
影响因子：
64.5
作者：
Guenther, Matthew G.;Levine, Stuart S.;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
6.6
作者：
Brown, Alan S.;Patterson, Paul H.
通讯作者：
Patterson, Paul H.