Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, California; MIND Institute, University of California, Davis, Davis, California.
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, California.
Biol Psychiatry. 2022 Sep 15;92(6):460-469. doi: 10.1016/j.biopsych.2022.04.004. Epub 2022 Apr 21.
Late adolescence is a period of dynamic change in the brain as humans learn to navigate increasingly complex environments. In particular, prefrontal cortical (PFC) regions undergo extensive remodeling as the brain is fine-tuned to orchestrate cognitive control over attention, reasoning, and emotions. Late adolescence also presents a uniquely vulnerable period as neurodevelopmental illnesses, such as schizophrenia, become evident and worsen into young adulthood. Challenges in early development, including prenatal exposure to infection, may set the stage for a cascade of maladaptive events that ultimately result in aberrant PFC connectivity and function before symptoms emerge. A growing body of research suggests that activation of the mother's immune system during pregnancy may act as a disease primer, in combination with other environmental and genetic factors, contributing to an increased risk of neurodevelopmental disorders, including schizophrenia. Animal models provide an invaluable opportunity to examine the course of brain and behavioral changes in offspring exposed to maternal immune activation (MIA). Although the vast majority of MIA research has been carried out in rodents, here we highlight the translational utility of the nonhuman primate (NHP) as a model species more closely related to humans in PFC structure and function. In this review, we consider the protracted period of brain and behavioral maturation in the NHP, describe emerging findings from MIA NHP offspring in the context of rodent preclinical models, and lastly explore the translational relevance of the NHP MIA model to expand understanding of the etiology and developmental course of PFC pathology in schizophrenia.
青少年晚期是大脑发生动态变化的时期,人类在此期间学会应对日益复杂的环境。特别是,前额皮质(prefrontal cortex,PFC)区域经历了广泛的重塑,因为大脑正在微调以协调对注意力、推理和情绪的认知控制。青少年晚期也是一个独特的脆弱时期,因为神经发育疾病(如精神分裂症)开始显现并在成年早期恶化。早期发育中的挑战,包括产前感染暴露,可能为一连串适应性不良事件奠定基础,最终导致异常的 PFC 连接和功能,而在此之前症状尚未出现。越来越多的研究表明,怀孕期间母亲免疫系统的激活可能作为疾病的启动因素,与其他环境和遗传因素一起,导致神经发育障碍(包括精神分裂症)的风险增加。动物模型为研究母体免疫激活(maternal immune activation,MIA)暴露后代的大脑和行为变化过程提供了宝贵的机会。尽管绝大多数 MIA 研究都是在啮齿动物中进行的,但在这里我们强调了非人类灵长类动物(nonhuman primate,NHP)作为一种与人类在 PFC 结构和功能上更为相似的模型物种的转化应用。在这篇综述中,我们考虑了 NHP 大脑和行为成熟的漫长过程,描述了 MIA NHP 后代在啮齿动物临床前模型背景下的新发现,并最后探讨了 NHP MIA 模型的转化相关性,以扩展对精神分裂症 PFC 病理学的病因和发育过程的理解。