Winter Christine, Reutiman Teri J, Folsom Timothy D, Sohr Reinhard, Wolf Rainer J, Juckel Georg, Fatemi S Hossein
Department of Psychiatry, Charite, Campus Mitte, Berlin, Germany.
Eur Neuropsychopharmacol. 2008 Oct;18(10):712-6. doi: 10.1016/j.euroneuro.2008.06.001. Epub 2008 Aug 6.
Prenatal viral infection has been associated with neurodevelopmental disorders such as schizophrenia and autism. It has previously been demonstrated that viral infection causes deleterious effects on brain structure and function in mouse offspring following late first trimester (E9) and middle-late second trimester (E18) administration of influenza virus. Neurochemical analysis following infection on E18 using this model has revealed significantly altered levels of serotonin, 5-hydroxyindoleacetic acid, and taurine, but not dopamine. In order to monitor these different patterns of monoamine expression in exposed offspring in more detail and to see if there are changes in the dopamine system at another time point, pregnant C57BL6J mice were infected with a sublethal dose of human influenza virus or sham-infected using vehicle solution on E16. Male offspring of the infected mice were collected at P0, P14, and P56, their brains removed and cerebellum dissected and flash frozen. Dopamine and serotonin levels were then measured using HPLC-ED technique. When compared to controls, there was a significant decrease in serotonin levels in the cerebella of offspring of virally exposed mice at P14. No differences in levels of dopamine were observed in exposed and control mice, although there was a significant decrease in dopamine at P14 and P56 when compared to P0. The present study shows that the serotonergic system is disrupted following prenatal viral infection, potentially modelling disruptions that occur in patients with schizophrenia and autism.
产前病毒感染与精神分裂症和自闭症等神经发育障碍有关。先前已经证明，在孕早期晚期（E9）和孕中期晚期（E18）给予流感病毒后，病毒感染会对小鼠后代的脑结构和功能产生有害影响。使用该模型在E18感染后进行的神经化学分析显示，血清素、5-羟吲哚乙酸和牛磺酸水平发生了显著变化，但多巴胺水平未变。为了更详细地监测暴露后代中这些不同的单胺表达模式，并查看在另一个时间点多巴胺系统是否有变化，在E16时，将怀孕的C57BL6J小鼠感染亚致死剂量的人类流感病毒或用赋形剂溶液进行假感染。在出生后第0天（P0）、第14天（P14）和第56天（P56）收集感染小鼠的雄性后代，取出它们的大脑，解剖小脑并速冻。然后使用高效液相色谱-电化学检测（HPLC-ED）技术测量多巴胺和血清素水平。与对照组相比，病毒暴露小鼠后代在P14时小脑内的血清素水平显著降低。在暴露组和对照组小鼠中未观察到多巴胺水平的差异，尽管与P0相比，P14和P56时多巴胺水平显著降低。本研究表明，产前病毒感染后血清素能系统受到破坏，这可能模拟了精神分裂症和自闭症患者中发生的破坏情况。
