Center for Neuroscience, UC Davis.
Center for Neuroscience, UC Davis;
J Vis Exp. 2022 Aug 17(186). doi: 10.3791/64095.
Maternal immune activation (MIA) during pregnancy is consistently linked to increased risk of neurodevelopmental and neuropsychiatric disorders in offspring. Animal models of MIA are used to test causality, investigate mechanisms, and develop diagnostics and treatments for these disorders. Despite their widespread use, many MIA models suffer from a lack of reproducibility and almost all ignore two important aspects of this risk factor: (i) many offspring are resilient to MIA, and (ii) susceptible offspring can exhibit distinct combinations of phenotypes. To increase reproducibility and model both susceptibility and resilience to MIA, the baseline immunoreactivity (BIR) of female mice before pregnancy is used to predict which pregnancies will result in either resilient offspring or offspring with defined behavioral and molecular abnormalities after exposure to MIA. Here, a detailed method of inducing MIA via intraperitoneal (i.p.) injection of the double stranded RNA (dsRNA) viral mimic poly(I:C) at 12.5 days of gestation is provided. This method induces an acute inflammatory response in the dam, which results in perturbations in brain development in mice that map onto similarly impacted domains in human psychiatric and neurodevelopmental disorders (NDDs).
母体免疫激活（MIA）在怀孕期间与后代神经发育和神经精神疾病的风险增加密切相关。MIA 的动物模型用于测试因果关系、研究机制，并开发这些疾病的诊断和治疗方法。尽管它们被广泛使用，但许多 MIA 模型存在缺乏重现性的问题，几乎所有模型都忽略了这种风险因素的两个重要方面：（i）许多后代对 MIA 有抵抗力，（ii）易感后代可以表现出不同的表型组合。为了提高重现性并模拟 MIA 的易感性和抵抗力，在怀孕前使用雌性小鼠的基础免疫反应性（BIR）来预测哪些妊娠将导致具有定义行为和分子异常的后代，或在暴露于 MIA 后具有抵抗能力的后代。在这里，提供了一种通过在妊娠第 12.5 天腹膜内（i.p.）注射双链 RNA（dsRNA）病毒模拟物聚（I：C）诱导 MIA 的详细方法。这种方法在母体中诱导急性炎症反应，导致小鼠大脑发育受到干扰，这与人类精神和神经发育障碍（NDD）中受同样影响的区域相对应。
