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全基因组表达分析揭示慢性精神分裂症中髓鞘形成相关基因的失调。

Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia.

作者信息

Hakak Y, Walker J R, Li C, Wong W H, Davis K L, Buxbaum J D, Haroutunian V, Fienberg A A

机构信息

Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.

出版信息

Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4746-51. doi: 10.1073/pnas.081071198.

Abstract

Neuropathological and brain imaging studies suggest that schizophrenia may result from neurodevelopmental defects. Cytoarchitectural studies indicate cellular abnormalities suggestive of a disruption in neuronal connectivity in schizophrenia, particularly in the dorsolateral prefrontal cortex. Yet, the molecular mechanisms underlying these findings remain unclear. To identify molecular substrates associated with schizophrenia, DNA microarray analysis was used to assay gene expression levels in postmortem dorsolateral prefrontal cortex of schizophrenic and control patients. Genes determined to have altered expression levels in schizophrenics relative to controls are involved in a number of biological processes, including synaptic plasticity, neuronal development, neurotransmission, and signal transduction. Most notable was the differential expression of myelination-related genes suggesting a disruption in oligodendrocyte function in schizophrenia.

摘要

神经病理学和脑成像研究表明,精神分裂症可能源于神经发育缺陷。细胞结构研究表明,精神分裂症存在细胞异常,提示神经元连接中断,尤其是在背外侧前额叶皮层。然而,这些发现背后的分子机制仍不清楚。为了识别与精神分裂症相关的分子底物,采用DNA微阵列分析来检测精神分裂症患者和对照患者死后背外侧前额叶皮层的基因表达水平。相对于对照组,在精神分裂症患者中确定表达水平发生改变的基因涉及许多生物学过程,包括突触可塑性、神经元发育、神经传递和信号转导。最值得注意的是与髓鞘形成相关基因的差异表达,这表明精神分裂症中少突胶质细胞功能受到破坏。

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