Oligodendrocyte dysfunction in schizophrenia and bipolar disorder
Oligodendrocyte dysfunction in schizophrenia and bipolar disorder
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DOI：
10.1016/s0140-6736(03)14289-4
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发表时间：
2003-09-06
期刊：
影响因子：
168.9
通讯作者：
Bahn, S
中科院分区：
文献类型：
--
作者：
Tkachev, D;Mimmack, ML;Bahn, S
背景阵列研究的结果表明，精神分裂症患者的脂质和髓鞘相关基因表达异常。在这里，我们研究了少突胶质细胞特异性和髓鞘相关基因在精神分裂症和双相情感障碍中的表达。方法我们使用Stanley脑收集的样本，包括15例精神分裂症，15例双相情感障碍和15个对照大脑。基于索引的差异显示聚合酶链式反应被用来筛选精神分裂症患者和对照组之间的基因表达差异。结果用定量聚合酶链式反应进行了交叉验证，该方法还被用于研究其他16个少突胶质细胞和髓鞘基因在精神分裂症和双相情感障碍中的表达谱。这些基因通过正在进行的微阵列分析进一步研究。差异显示和定量PCR分析的结果显示，精神分裂症和双相情感障碍患者关键的少突胶质细胞相关基因和髓鞘相关基因减少；这两种疾病的表达变化显示出高度重叠。通过定量聚合酶链式反应研究的相同基因的微阵列结果总体上具有很好的相关性。与对照大脑相比，解释性精神分裂症和双相情感障碍大脑显示关键的少突胶质细胞和髓鞘形成基因的下调，包括调节这些基因的转录因子。这些结果支持并扩展了其他微阵列研究的观察结果。我们的研究还显示了与精神分裂症组相似的双相大脑表达变化，从而支持了这种疾病具有共同的病因和病理生理途径的观点。
Background Results of array studies have suggested abnormalities in expression of lipid and myelin-related genes in schizophrenia. Here, we investigated oligodendrocyte-specific and myelination-associated gene expression in schizophrenia and bipolar affective disorder.Methods We used samples from the Stanley brain collection, consisting of 15 schizophrenia, 15 bipolar affective disorder, and 15 control brains. Indexing-based differential display PCR was done to screen for differences in gene expression in schizophrenia patients versus controls. Results were cross-validated with quantitative PCR,, which was also used to investigate expression profiles of 16 other oligodendrocyte and myelin genes in schizophrenia and bipolar disorder. These genes were further investigated with an ongoing microarray analysis.Findings Results of differential display and quantitative PCR analysis showed a reduction of key oligodendrocyte-related and myelin-related genes in schizophrenia and bipolar patients; expression changes for both disorders showed a high degree of overlap. Microarray results of the same genes investigated by quantitative PCR correlated well overall.Interpretation Schizophrenia and bipolar brains showed downregulation of key oligodendrocyte and myelination genes, including transcription factors that regulate these genes, compared with control brains. These results lend support to and extend observations from other microarray investigations. Our study also showed similar expression changes to the schizophrenia group in bipolar brains, which thus lends support to the notion that the disorders share common causative and pathophysiological pathways.