Fatemi S Hossein, Folsom Timothy D, Reutiman Teri J, Sidwell Robert W
Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, 420 Delaware Ave SE, MMC 392, Minneapolis, MN 55455, USA.
Schizophr Res. 2008 Jan;98(1-3):163-77. doi: 10.1016/j.schres.2007.09.031. Epub 2007 Nov 9.
The current study investigated whether human influenza viral infection in midpregnancy leads to alterations in proteins involved in brain development. Human influenza viral infection was administered to E9 pregnant Balb/c mice. Brains of control and virally-exposed littermates were subjected to microarray analysis, SDS-PAGE and western blotting at three postnatal stages. Microarray analysis of virally-exposed mouse brains showed significant, two-fold change in expression of multiple genes in both neocortex and cerebellum when compared to sham-infected controls. Levels of mRNA and protein levels of four selected genes were examined in brains of exposed mice. Nucleolin mRNA was significantly decreased in day 0 and day 35 neocortex and significantly increased in day 35 cerebellum. Protein levels were significantly upregulated at days 35 and 56 in neocortex and at day 56 in cerebellum. Connexin 43 protein levels were significantly decreased at day 56 in neocortex. Aquaporin 4 mRNA was significantly decreased in day 0 neocortex. Aquaporin 4 protein levels decreased in neocortex significantly at day 35. Finally, microcephalin mRNA was significantly decreased in day 56 neocortex and protein levels were significantly decreased at 56 cerebellum. These data suggest that influenza viral infection in midpregnancy in mice leads to long-term changes in brain markers for enhanced ribosome genesis (nucleolin), increased production of immature neurons (microcephalin), and abnormal glial-neuronal communication and neuron migration (connexin 43 and aquaporin 4).
本研究调查了孕期中期的人类流感病毒感染是否会导致参与大脑发育的蛋白质发生改变。将人类流感病毒感染E9期的怀孕Balb/c小鼠。在三个出生后阶段,对对照组和病毒暴露组同窝小鼠的大脑进行微阵列分析、SDS-PAGE和蛋白质印迹分析。与假感染对照组相比,病毒暴露小鼠大脑的微阵列分析显示,新皮层和小脑中多个基因的表达有显著的两倍变化。在暴露小鼠的大脑中检测了四个选定基因的mRNA水平和蛋白质水平。核仁素mRNA在出生后0天和35天的新皮层中显著降低,在出生后35天的小脑中显著增加。蛋白质水平在出生后35天和56天的新皮层中以及出生后56天的小脑中显著上调。连接蛋白43的蛋白质水平在出生后56天的新皮层中显著降低。水通道蛋白4 mRNA在出生后0天的新皮层中显著降低。水通道蛋白4的蛋白质水平在出生后35天的新皮层中显著降低。最后,小头畸形蛋白mRNA在出生后56天的新皮层中显著降低,蛋白质水平在出生后56天的小脑中显著降低。这些数据表明,小鼠孕期中期的流感病毒感染会导致大脑标志物的长期变化,这些变化涉及增强核糖体生成(核仁素)、增加未成熟神经元的产生(小头畸形蛋白)以及异常的胶质-神经元通讯和神经元迁移(连接蛋白43和水通道蛋白4)。