Differential display analysis of gene expression in brains from hepatitis C-infected patients.
Differential display analysis of gene expression in brains from hepatitis C-infected patients.
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丙型肝炎感染患者大脑基因表达的差异显示分析。
DOI：
10.1097/01.aids.0000192084.79679.e4
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Laskus,Tomasz
中科院分区：
文献类型：
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作者：
Adair,DebraM;Radkowski,Marek;Jablonska,Joanna;Pawelczyk,Agnieszka;Wilkinson,Jeffrey;Rakela,Jorge;Laskus,Tomasz
目的：丙型肝炎病毒（HCV）感染常与认知功能障碍、疲劳和抑郁有关。目前的研究进行，以确定是否HCV感染影响脑组织中的基因expression.Design：我们分析了一组HCV感染患者的脑组织中的基因表达模式与HCV阴性controls.Methods：脑组织标本在尸检中获得从三个HCV阳性患者和三个HCV阴性对照患者。采用差异显示和反向北方杂交进行基因表达分析。结果：经差异显示和反向北方杂交，共鉴定出29个差异表达基因。一个突出的发现是HCV感染患者线粒体氧化磷酸化基因的下调。脑氧化/能量代谢的损伤以前被认为是许多损害精神状态的疾病的近因。另一个发现是下调的一些核糖体蛋白基因和几个基因参与转录调控，可能反映了减少代谢activity.Conclusion：我们的研究结果表明，第一次，可能有一个生物学基础的神经精神症状和认知障碍与HCV感染。
Objectives:Hepatitis C virus (HCV) infection is often associated with cognitive dysfunction, fatigue and depression. The current study was undertaken to determine whether HCV infection affects gene expression in brain tissue.Design:We analysed the gene expression pattern in brain tissue in a group of HCV-infected patients compared with HCV-negative controls.Methods:Brain tissue samples were obtained at autopsy from three HCV-positive patients and three HCV-negative control patients. The analysis of gene expression was conducted using differential display and reverse Northern hybridization. Only those genes that were up or downregulated more than 1.8 times were considered to be differentially expressed.Results:Altogether, 29 differentially expressed genes were identified by differential display and subsequently confirmed by reverse Northern hybridization. A prominent finding was the downregulation of mitochondrial oxidative phosphorylation genes in HCV-infected patients. The impairment of brain oxidative/energy metabolism has previously been suggested to be the proximate cause of many disorders that impair mentation. Another finding was the downregulation of some ribosomal protein genes and several genes involved in transcription regulation, perhaps reflecting reduced metabolic activities.Conclusion:Our findings suggest for the first time that there may be a biological basis for the neuropsychiatric symptoms and cognitive impairment associated with HCV infection.