Meyer Urs, Feldon Joram
Laboratory of Behavioural Neurobiology, ETH Zurich, Schorenstrasse 16, Schwerzenbach 8603, Switzerland.
Behav Brain Res. 2009 Dec 7;204(2):322-34. doi: 10.1016/j.bbr.2008.12.022. Epub 2008 Dec 30.
Maternal infection during pregnancy is a notable risk factor for the offspring to develop severe neuropsychiatric disorders, including schizophrenia. One prevalent hypothesis suggests that infection-induced disruption of early prenatal brain development predisposes the organism for long-lasting structural and functional brain abnormalities, leading to the emergence of psychopathological behaviour in adulthood. The feasibility of this causal link has received considerable support from several experimental models established in both rats and mice. In this review, we provide an integrative summary of the long-term neuropathological consequences of prenatal exposure to infection and/or inflammation as identified in various experimental models of prenatal immune challenge. In addition, we highlight how abnormalities in distinct brain areas and neurotransmitter systems following prenatal immune activation may provide a neural basis for the emergence of specific forms of psychosis-related behaviour. Specifically, we suggest that prenatal infection-induced imbalances in the mesolimibic and mesocortical dopamine pathways may constitute critical neural mechanisms for disturbances in sensorimotor gating, abnormalities in selective associative learning and hypersensitivity to psychostimulant drugs. On the other hand, the emergence of working memory deficiency following prenatal immune challenge may be crucially linked to the concomitant disruption of GABAergic and glutamatergic functions in prefrontal cortical and hippocampal structures. Notably, many of the identified neuronal abnormalities are directly implicated in the neuropathology of schizophrenia. The findings from prenatal infection models of schizophrenia thus provide considerable experimental evidence for the assumption that prenatal exposure to infection and/or inflammation is a relevant environmental link to specific neuronal abnormalities underlying psychosis-related behaviour in humans.
孕期母体感染是后代患严重神经精神疾病（包括精神分裂症）的一个显著风险因素。一种普遍的假说是，感染引起的早期产前脑发育中断使机体易出现长期的脑结构和功能异常，从而导致成年期精神病理行为的出现。这种因果关系的可行性已在大鼠和小鼠建立的多个实验模型中得到了相当多的支持。在本综述中，我们综合总结了在各种产前免疫挑战实验模型中所确定的产前暴露于感染和/或炎症的长期神经病理学后果。此外，我们强调产前免疫激活后不同脑区和神经递质系统的异常如何可能为特定形式的精神病相关行为的出现提供神经基础。具体而言，我们认为产前感染引起的中脑边缘和中脑皮质多巴胺通路失衡可能是感觉运动门控障碍、选择性联想学习异常和对精神兴奋剂药物过敏的关键神经机制。另一方面，产前免疫挑战后工作记忆缺陷的出现可能与前额叶皮质和海马结构中γ-氨基丁酸能和谷氨酸能功能的同时破坏密切相关。值得注意的是，许多已确定的神经元异常直接与精神分裂症的神经病理学有关。因此，精神分裂症产前感染模型的研究结果为以下假设提供了大量实验证据：产前暴露于感染和/或炎症是与人类精神病相关行为背后特定神经元异常相关的环境因素。
