Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder
Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder
复制标题
DOI：
10.1038/sj.mp.4001565
复制
发表时间：
2005-03-01
影响因子：
11
通讯作者：
Sokolov, BP
中科院分区：
文献类型：
--
作者：
Aston, C;Jiang, L;Sokolov, BP
重度抑郁症是最常见和最具破坏性的精神疾病之一。为了确定重度抑郁症的候选机制，我们使用Affytelium HgU 95 A微阵列比较了12名重度抑郁症患者和14名匹配对照的颞叶皮层基因表达。在神经发育、信号转导和细胞通讯相关基因家族中发现了显著的表达变化。其中，17个与少突胶质细胞功能相关的基因的表达在抑郁症患者中显著降低（P1.4）。这17个基因中的8个编码髓磷脂的结构组分（CNP、MAG、MAL、MOG、MOBP、PMP 22、PLLP、PLP 1）。其他五个基因编码参与髓鞘成分合成的酶（ASPA，UGT 8），或者在髓鞘形成的调节中是必需的（ENPP 2，EDG 2，TF，KLK 6）。一个基因，即SOX 10，编码调节其他髓鞘形成相关基因的转录因子。0 LIG 2是仅存在于少突胶质细胞和少突胶质细胞前体中的转录因子。另一个基因ERBB 3参与少突胶质细胞分化。除了髓鞘形成相关基因外，参与轴突生长/突触功能的多个基因也发生了显著变化。这些发现表明，重度抑郁症可能与细胞通讯和信号转导机制的变化有关，这些机制导致少突胶质细胞和突触功能异常。与其他研究一起，这些发现表明，重性抑郁症可能与精神分裂症和双相情感障碍有共同的少突胶质细胞异常。
Major depressive disorder is one of the most common and devastating psychiatric disorders. To identify candidate mechanisms for major depressive disorder, we compared gene expression in the temporal cortex from 12 patients with major depressive disorder and 14 matched controls using Affymetrix HgU95A microarrays. Significant expression changes were revealed in families of genes involved in neurodevelopment, signal transduction and cell communication. Among these, the expression of 17 genes related to oligodendrocyte function was significantly (P1.4) decreased in patients with major depressive disorder. Eight of these 17 genes encode structural components of myelin (CNP, MAG, MAL, MOG, MOBP, PMP22, PLLP, PLP1). Five other genes encode enzymes involved in the synthesis of myelin constituents (ASPA, UGT8), or are essential in regulation of myelin formation (ENPP2, EDG2, TF, KLK6). One gene, that is, SOX10, encodes a transcription factor regulating other myelination-related genes. OLIG2 is a transcription factor present exclusively in oligodendrocytes and oligodendrocyte precursors. Another gene, ERBB3, is involved in oligodendrocyte differentiation. In addition to myelination-related genes, there were significant changes in multiple genes involved in axonal growth/synaptic function. These findings suggest that major depressive disorder may be associated with changes in cell communication and signal transduction mechanisms that contribute to abnormalities in oligodendroglia and synaptic function. Taken together with other studies, these findings indicate that major depressive disorder may share common oligodendroglial abnormalities with schizophrenia and bipolar disorder.