The suppression of maternal-fetal leukemia inhibitory factor signal relay pathway by maternal immune activation impairs brain development in mice.
The suppression of maternal-fetal leukemia inhibitory factor signal relay pathway by maternal immune activation impairs brain development in mice.
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DOI：
10.1371/journal.pone.0129011
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hatta T
中科院分区：
文献类型：
--
作者：
Tsukada T;Simamura E;Shimada H;Arai T;Higashi N;Akai T;Iizuka H;Hatta T
最近在啮齿动物中的研究表明，病毒感染引起的母体免疫激活（MIA）与后代的精神分裂症和自闭症有关。虽然母体IL-6被认为是MIA诱发这些神经精神障碍的可能介质，但其机制仍有待阐明。以前，我们报道了母体白血病抑制因子（LIF）-胎盘促肾上腺皮质激素-胎儿LIF信号传递途径（母胎LIF信号传递）促进大鼠胎儿大脑神经发生。在这里，我们报告说，母胎LIF信号中继在小鼠中被抑制注射到母鼠的多核糖肌苷酸，多核糖胞苷酸，诱导MIA在12.5天后coadministration。母血IL-6水平和胎盘细胞因子信号转导抑制因子3（Socs 3）基因表达随MIA严重程度增加而增加，胎盘Socs 3基因表达与母血IL-6水平相关。此外，我们发现MIA导致胎儿脑脊液中LIF水平降低，导致大脑神经发生减少。这些发现表明，母体IL-6通过诱导胎盘中的SOCS 3干扰母胎LIF信号传递，并导致神经发生减少。
Recent studies in rodents suggest that maternal immune activation (MIA) by viral infection is associated with schizophrenia and autism in offspring. Although maternal IL-6 is though t to be a possible mediator relating MIA induced these neuropsychiatric disorders, the mechanism remains to be elucidated. Previously, we reported that the maternal leukemia inhibitory factor (LIF)–placental ACTH–fetal LIF signaling relay pathway (maternal–fetal LIF signal relay) promotes neurogenesis of fetal cerebrum in rats. Here we report that the maternal–fetal LIF signal relay in mice is suppressed by injection of polyriboinosinic-polyribocytidylic acid into dams, which induces MIA at 12.5 days post-coitum. Maternal IL-6 levels and gene expression of placental suppressor of cytokine signaling 3 (Socs3) increased according to the severity of MIA and gene expression of placental Socs3 correlated with maternal IL-6 levels. Furthermore, we show that MIA causes reduction of LIF level in the fetal cerebrospinal fluid, resulting in the decreased neurogenesis in the cerebrum. These findings suggest that maternal IL-6 interferes the maternal–fetal LIF signal relay by inducing SOCS3 in the placenta and leads to decreased neurogenesis.
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影响因子：
2
作者：
Gundersen, HJG;Jensen, EBV;Nielsen, J
通讯作者：
Nielsen, J
影响因子：
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作者：
Auernhammer, CJ;Chesnokova, V;Melmed, S
通讯作者：
Melmed, S
影响因子：
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作者：
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Feldon, J
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3.8
作者：
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Godfrey, KM
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作者：
Farkas, Lilla M.;Huttner, Wieland B.
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Huttner, Wieland B.