Gene expression differences in bipolar disorder revealed by cDNA array analysis of post-mortem frontal cortex
Gene expression differences in bipolar disorder revealed by cDNA array analysis of post-mortem frontal cortex
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DOI：
10.1046/j.1471-4159.2001.00628.x
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发表时间：
2001-11-01
影响因子：
4.7
通讯作者：
Young, LT
中科院分区：
文献类型：
--
作者：
Bezchlibnyk, YB;Wang, JF;Young, LT
先前的研究表明双相情感障碍（BD）的病因涉及多种生化途径。然而，这种疾病的确切异常情况仍有待确定。为了研究在双相情感障碍病理生理学中可能起重要作用的新因素，我们利用cDNA表达阵列来检测多达1200个已知参与潜在相关生化过程的基因的表达差异。这项研究是在来自双相情感障碍患者和匹配对照的额叶皮质组织的尸检样本中进行的，样本（每组n = 10）来自斯坦利基金会神经病理学联盟。结果包括在一些基因（n = 24）中双相情感障碍组和对照组之间存在显著（信号强度变化大于35%）差异。通过逆转录聚合酶链反应（RT - PCR）对选定的目标进行分析，结果证实双相情感障碍中转化生长因子 - β1（TGF - β1）减少，半胱天冬酶 - 8前体（casp - 8）和erbB2转导蛋白（Tob）表达增加。我们通过逆转录聚合酶链反应在单个尸检样本中进一步观察到双相情感障碍中TGF - β1 mRNA水平显著降低。鉴于这种抑制性细胞因子具有神经保护作用，我们的结果表明TGF - β1的下调可能导致各种神经毒性损伤，这些损伤可能与某些情绪障碍的病因有关。
Previous studies have implicated a number of biochemical pathways in the etiology of bipolar disorder (BD). However, the precise abnormalities underlying this disorder remain to be established. To investigate novel factors that may be important in the pathophysiology of BD, we utilized cDNA expression arrays to examine differences in expression of up to 1200 genes known to be involved in potentially relevant biochemical processes. This investigation was undertaken in post-mortem samples of frontal cortex tissue from patients with BD and matched controls, obtained (n = 10/group) from the Stanley Foundation Neuropathology Consortium. Results include significant (greater than 35% change in signal intensity) differences between BD and controls in a number of genes (n = 24). Selected targets were analyzed by RT-PCR, which confirmed a decrease in transforming growth factor-beta1 (TGF-beta1), and an increase in both caspase-8 precursor (casp-8) and transducer of erbB2 (Tob) expression in BD. We further observed a significant decrease of TGF-beta1 mRNA levels in BD by RT-PCR in individual post-mortem samples. Given the neuroprotective role attributed to this inhibitory cytokine, our results suggest that the downregulation of TGF-beta1 may lead to various neurotoxic insults potentially involved in the etiology of certain mood disorders.