首页> 外文期刊>Neuroscience Letters: An International Multidisciplinary Journal Devoted to the Rapid Publication of Basic Research in the Brain Sciences >Altered expression of pro-inflammatory and developmental genes in the fetal brain in a mouse model of maternal infection.
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Altered expression of pro-inflammatory and developmental genes in the fetal brain in a mouse model of maternal infection.

机译:母体感染小鼠模型中胎儿脑中促炎和发育基因的表达改变。

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Human studies of unexplained cerebral palsy (CP) suggest an association with maternal infection. We used an established model of maternal infection, lipopolysaccharide (LPS) administration, to investigate the molecular changes in the fetal brain that may link maternal infection and CP. We compared gene expression in brains from mouse pups exposed to LPS in utero to those from saline-treated controls. Dams were injected with 50 microg LPS or saline on E18 with surgical delivery from 0.5 to 6h later. Differential gene expression was analyzed in the whole mouse brain using RT-PCR. When compared to control mice, pups exposed to LPS showed increased expression of pro-inflammatory genes monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and interleukin-1beta (IL-1beta), as well as VEGF, a regulator of vascular development and permeability, the anti-apoptotic protein Y-box-binding protein-1 (YB-1), and the neuronal differentiation factor necdin. LPS-exposed mice also showed downregulation of semaphorin 5b and groucho, involved in axon guidance and neurogenesis, respectively, providing evidence that LPS may disrupt normal developmental pathways. These data suggest possible mechanisms for adverse neurological outcomes following maternal infection involving elevated cytokine levels and altered expression of developmental genes in the fetal brain.
机译:对无法解释的脑瘫(CP)的人体研究表明,它与母亲感染有关。我们使用了建立的孕产妇感染模型,即脂多糖(LPS)管理,以研究胎儿脑中可能与孕产妇感染和CP相关的分子变化。我们比较了小鼠子宫内暴露于LPS的幼仔与盐水处理对照组的大脑中的基因表达。在E18上向大坝注射50 microg LPS或盐水,并在0.5至6h后进行手术。使用RT-PCR分析整个小鼠大脑中的差异基因表达。与对照组小鼠相比,暴露于LPS的幼犬还表现出促炎基因单核细胞趋化蛋白1(MCP-1),白细胞介素6(IL-6)和白细胞介素1beta(IL-1beta)的表达增加。作为VEGF,它是血管发育和通透性的调节剂,抗凋亡蛋白Y-box-binding protein-1(YB-1)和神经元分化因子necdin。暴露于LPS的小鼠还显示出分别参与轴突引导和神经发生的信号蛋白5b和groucho的下调,提供了LPS可能破坏正常发育途径的证据。这些数据表明了母体感染后涉及胎儿细胞因子水平升高和胎儿大脑发育基因表达改变的不良神经系统预后的可能机制。

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