Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California Davis, Davis, California; California National Primate Research Center, University of California Davis, Davis, California.
Department of Psychiatry and Behavioral Sciences, MIND Institute, University of California Davis, Davis, California; California National Primate Research Center, University of California Davis, Davis, California.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2022 May;7(5):510-523. doi: 10.1016/j.bpsc.2022.02.012. Epub 2022 Mar 8.
Pregnant women represent a uniquely vulnerable population during an infectious disease outbreak, such as the COVID-19 pandemic. Although we are at the early stages of understanding the specific impact of SARS-CoV-2 exposure during pregnancy, mounting epidemiological evidence strongly supports a link between exposure to a variety of maternal infections and an increased risk for offspring neurodevelopmental disorders. Inflammatory biomarkers identified from archived or prospectively collected maternal biospecimens suggest that the maternal immune response is the critical link between infection during pregnancy and altered offspring neurodevelopment. This maternal immune activation (MIA) hypothesis has been tested in animal models by artificially activating the immune system during pregnancy and evaluating the neurodevelopmental consequences in MIA-exposed offspring. Although the vast majority of MIA model research is carried out in rodents, the nonhuman primate model has emerged in recent years as an important translational tool. In this review, we briefly summarize human epidemiological studies that have prompted the development of translationally relevant MIA models. We then highlight notable similarities between humans and nonhuman primates, including placental structure, pregnancy physiology, gestational timelines, and offspring neurodevelopmental stages, that provide an opportunity to explore the MIA hypothesis in species more closely related to humans. Finally, we provide a comprehensive review of neurodevelopmental alterations reported in current nonhuman primate models of maternal infection and discuss future directions for this promising area of research.
孕妇在传染病爆发期间，如 COVID-19 大流行期间，是一个独特的弱势群体。尽管我们还处于理解怀孕期间暴露于 SARS-CoV-2 对特定影响的早期阶段，但越来越多的流行病学证据强烈支持母体感染与后代神经发育障碍风险增加之间存在联系。从存档或前瞻性收集的母体生物样本中鉴定出的炎症生物标志物表明，母体免疫反应是感染与后代神经发育改变之间的关键联系。这种母体免疫激活（MIA）假说已在动物模型中得到检验，方法是在怀孕期间人为激活免疫系统，并评估 MIA 暴露后代的神经发育后果。尽管绝大多数 MIA 模型研究都是在啮齿动物中进行的，但近年来，非人类灵长类动物模型已成为一种重要的转化工具。在这篇综述中，我们简要总结了促使开发具有转化相关性的 MIA 模型的人类流行病学研究。然后，我们突出了人类和非人类灵长类动物之间的显著相似之处，包括胎盘结构、妊娠生理学、妊娠时间线和后代神经发育阶段，为在与人类更相关的物种中探索 MIA 假说提供了机会。最后，我们全面回顾了目前母体感染的非人类灵长类动物模型中报告的神经发育改变，并讨论了这一有前途的研究领域的未来方向。
