Department of Psychiatry, Vanderbilt University, Nashville, TN 37203, USA.
Transl Psychiatry. 2012 Apr 3;2(4):e98. doi: 10.1038/tp.2012.24.
We are exploring the mechanisms underlying how maternal infection increases the risk for schizophrenia and autism in the offspring. Several mouse models of maternal immune activation (MIA) were used to examine the immediate effects of MIA induced by influenza virus, poly(I:C) and interleukin IL-6 on the fetal brain transcriptome. Our results indicate that all three MIA treatments lead to strong and common gene expression changes in the embryonic brain. Most notably, there is an acute and transient upregulation of the α, β and γ crystallin gene family. Furthermore, levels of crystallin gene expression are correlated with the severity of MIA as assessed by placental weight. The overall gene expression changes suggest that the response to MIA is a neuroprotective attempt by the developing brain to counteract environmental stress, but at a cost of disrupting typical neuronal differentiation and axonal growth. We propose that this cascade of events might parallel the mechanisms by which environmental insults contribute to the risk of neurodevelopmental disorders such as schizophrenia and autism.
我们正在探索母体感染如何增加后代患精神分裂症和自闭症风险的机制。使用了几种母体免疫激活 (MIA) 的小鼠模型，以研究流感病毒、聚肌苷酸：聚胞苷酸 (poly(I:C)) 和白细胞介素 IL-6 诱导的 MIA 对胎儿大脑转录组的即时影响。我们的结果表明，所有三种 MIA 处理都会导致胚胎大脑中强烈且常见的基因表达变化。最值得注意的是，α、β 和 γ 晶体蛋白基因家族的急性和短暂上调。此外，晶体蛋白基因表达水平与胎盘重量评估的 MIA 严重程度相关。总体基因表达变化表明，对 MIA 的反应是发育中大脑为对抗环境压力而进行的神经保护尝试，但代价是破坏典型的神经元分化和轴突生长。我们提出，这一连串事件可能类似于环境损伤导致精神分裂症和自闭症等神经发育障碍风险的机制。
