Physiology and Behavior Laboratory, Swiss Federal Institute of Technology (ETH) Zurich, Schwerzenbach, Switzerland.
Biol Psychiatry. 2014 Feb 15;75(4):307-15. doi: 10.1016/j.biopsych.2013.07.011. Epub 2013 Aug 12.
It is increasingly appreciated that altered neuroimmune mechanisms might play a role in the development of schizophrenia and related psychotic illnesses. On the basis of human epidemiological findings, a number of translational rodent models have been established to explore the consequences of prenatal immune activation on brain and behavioral development. The currently existing models are based on maternal gestational exposure to human influenza virus, the viral mimic polyriboinosinic-polyribocytidilic acid [Poly(I:C)], the bacterial endotoxin lipopolysaccharide, the locally acting inflammatory agent turpentine, or selected inflammatory cytokines. These models are pivotal for establishing causal relationships and for identifying cellular and molecular mechanisms that affect normal brain development in the event of early-life immune exposures. An important aspect of developmental immune activation models is that they allow a multi-faceted, longitudinal monitoring of the disease process as it unfolds during the course of neurodevelopment from prenatal to adult stages of life. An important recent refinement of these models is the incorporation of multiple etiologically relevant risk factors by combining prenatal immune challenges with specific genetic manipulations or additional environmental adversities. Converging findings from such recent experimental attempts suggest that prenatal infection can act as a "neurodevelopmental disease primer" that is likely relevant for a number of chronic mental illnesses. Hence, the adverse effects induced by prenatal infection might reflect an early entry into the neuropsychiatric route, but the specificity of subsequent disease or symptoms is likely to be strongly influenced by the genetic and environmental context in which the prenatal infectious process occurs.
人们越来越认识到，神经免疫机制的改变可能在精神分裂症和相关精神病的发生发展中起作用。基于人类的流行病学研究结果，已经建立了许多转化啮齿动物模型来探索产前免疫激活对大脑和行为发育的影响。目前现有的模型是基于母体妊娠期暴露于人流感病毒、病毒模拟物聚肌胞苷酸[Poly(I:C)]、细菌内毒素脂多糖、局部作用的炎症剂松节油或选定的炎症细胞因子。这些模型对于确定因果关系以及确定细胞和分子机制至关重要，这些机制在生命早期的免疫暴露影响正常大脑发育的情况下会产生影响。发育性免疫激活模型的一个重要方面是，它们允许在神经发育过程中从产前到成年阶段的疾病过程中进行多方面的、纵向监测。这些模型的一个重要的最新改进是通过将产前免疫挑战与特定的遗传操作或额外的环境逆境相结合，纳入多个与病因相关的风险因素。最近这些实验尝试的汇聚结果表明，产前感染可以作为一种“神经发育性疾病启动子”，可能与许多慢性精神疾病有关。因此，产前感染引起的不良反应可能反映了进入神经精神途径的早期阶段，但随后疾病或症状的特异性可能受到发生产前感染的遗传和环境背景的强烈影响。
