Correlation of transcriptome profile with electrical activity in temporal lobe epilepsy
Correlation of transcriptome profile with electrical activity in temporal lobe epilepsy
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DOI：
10.1016/j.nbd.2005.12.012
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发表时间：
2006-05-01
影响因子：
6.1
通讯作者：
DeFelipe, J
中科院分区：
文献类型：
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作者：
Arion, D;Sabatini, M;DeFelipe, J
人类癫痫大脑活动的生物学基础尚未得到很好的理解，可能取决于基因表达的变化。我们对12个前外侧颞叶皮质样本进行了微阵列转录组分析，这些样本来自5个患有颞叶癫痫至少10年的个体。在部分肺叶切除术之前，对每位患者的皮质表面进行术中皮质电描记术。这些记录显示频率和振幅的特征差异，定义为“尖峰”（异常）或“非尖峰”（正常）。在两个样本组的转录组中，转铁蛋白（TF）是差异表达最多的基因。此外，基因表达谱分析还显示，加标样品中多种GABA系统相关基因（GABRA 5、GABRB 3、ABAT）下调，少突胶质细胞和脂质代谢转录物（MOG、CA 2、CNP、SCD、PLP 1、FA 2 H、ABCA 2）上调。此外，与经典MAPK级联相关的几种转录物显示加标和非加标样品之间的表达水平变化（G3 BP 2、MAPK 1、PRKAR 1A和MAP 4K 4）。在选择用于通过RT qPCR验证的12个基因中，9个在微阵列预测的方向上显示出显著的表达变化。基因芯片检测结果与qPCR检测结果高度相关（r = 0.98; P < 0.001）。我们的结论是，在尖峰样品异常的脑电活动与基因表达的变化密切相关，我们推测，一些观察到的转录组的变化可能直接参与诱导或预防癫痫发作事件。(c)2005年爱思唯尔公司All rights reserved.
The biology underlying epileptic brain activity in humans is not well understood and likely depends on changes in gene expression. We performed a microarray transcriptome profiling of 12 anterolateral temporal cortical samples originating from five individuals who suffered with temporal lobe epilepsy for at least 10 years. Prior to partial lobectomy, intraoperative electrocorticography was performed on the cortical surface of each patient. These recordings showed characteristic differences in frequency and amplitude that were defined as "spiking" (abnormal) or "non-spiking" (normal). Between the transcriptome of the two sample groups, transferrin (TF) was the most differentially expressed gene. Furthermore, gene expression profiling also revealed a downregulation of multiple GABA system-related genes (GABRA5, GABRB3, ABAT) in the spiking samples and an upregulation of oligodendrocyte and lipid metabolism transcripts (MOG, CA2, CNP, SCD, PLP1, FA2H, ABCA2). In addition, several transcripts related to the classical MAPK cascade showed expression level alterations between the spiking and non-spiking samples (G3BP2, MAPK1, PRKAR1A, and MAP4K4). Out of 12 genes chosen for verification by RT qPCR, 9 showed significant expression changes in the microarray-predicted direction. Furthermore, the microarray and qPCR data were highly correlated (r = 0.98; P < 0.001). We conclude that abnormal electrical brain activity in the spiking samples is strongly correlated with gene expression changes and we speculate that some of the observed transcriptome changes may be directly involved in the induction or prevention of the ictal events seen in epilepsy. (c) 2005 Elsevier Inc. All rights reserved.