Chow Ke-Huan, Yan Zihao, Wu Wei-Li
Division of Biology and Biological Engineering, California Institute of Technology.
Division of Biology and Biological Engineering, California Institute of Technology; Harvard Medical School.
J Vis Exp. 2016 Mar 25(109):e53643. doi: 10.3791/53643.
Maternal immune activation (MIA) model is increasingly well appreciated as a rodent model for the environmental risk factor of various psychiatric disorders. Numerous studies have demonstrated that MIA model is able to show face, construct, and predictive validity that are relevant to autism and schizophrenia. To model MIA, investigators often use viral mimic polyinosinic:polycytidylic acid (poly(I:C)) to activate the immune system in pregnant rodents. Generally, the offspring from immune activated dam exhibit behavioral abnormalities and physiological alterations that are associated with autism and schizophrenia. However, poly(I:C) injection with different dosages and at different time points could lead to different outcomes by perturbing brain development at different stages. Here we provide a detailed method of inducing MIA by intraperitoneal (i.p.) injection of 20 mg/kg poly(I:C) at mid-gestational embryonic 12.5 days (E12.5). This method has been shown to induce acute inflammatory response in the maternal-placental-fetal axis, which ultimately results in the brain perturbations and behavioral phenotypes that are associated with autism and schizophrenia.
母体免疫激活（MIA）模型作为各种精神疾病环境风险因素的啮齿动物模型，越来越受到广泛认可。大量研究表明，MIA模型能够展现出与自闭症和精神分裂症相关的表面效度、结构效度和预测效度。为了构建MIA模型，研究人员通常使用病毒模拟物聚肌苷酸：聚胞苷酸（poly(I:C)）来激活怀孕啮齿动物的免疫系统。一般来说，免疫激活母鼠的后代会表现出与自闭症和精神分裂症相关的行为异常和生理改变。然而，在不同时间点注射不同剂量的poly(I:C)，可能会通过干扰不同发育阶段的大脑发育而导致不同的结果。在此，我们提供一种详细的方法，即在妊娠中期胚胎第12.5天（E12.5）通过腹腔注射20 mg/kg poly(I:C)来诱导MIA。该方法已被证明可在母胎-胎盘-胎儿轴诱导急性炎症反应，最终导致与自闭症和精神分裂症相关的大脑紊乱和行为表型。
