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蛋白质组学分析揭示了精神分裂症患者脑岛皮质第2层内的蛋白质变化。

Proteomic analysis reveals protein changes within layer 2 of the insular cortex in schizophrenia.

作者信息

Pennington Kyla, Dicker Patrick, Dunn Michael J, Cotter David R

机构信息

Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland.

出版信息

Proteomics. 2008 Dec;8(23-24):5097-107. doi: 10.1002/pmic.200800415.

Abstract

Abnormalities in the size and activity of the insular cortex (IC), a brain region involved in auditory hallucinations and language, have been previously found in brain imaging studies in schizophrenia. In addition, cortical layer 2 has been shown to be abnormal in many brain regions in schizophrenia. In this study, 2-D DIGE was used to quantitatively analyse protein expression in schizophrenia and control cases (n = 15/group) in microdissected layer 2 IC tissue. Proteomic analyses revealed 57 significantly differentially expressed (p<0.05) protein spots in schizophrenia. Validation of differential expression of two of the proteins differentially expressed was subsequently confirmed using Western blotting. This work provides evidence of abnormal protein expression in layer 2 of the IC in schizophrenia, supporting previous work of reduced neuronal size in this cortical layer in the IC. Over half of proteins abnormally expressed in this study have not been reported previously in proteomic studies investigating schizophrenia or neurodegenerative disorders. Proteins found to be abnormally expressed appear to collectively impact on neuronal plasticity through roles in neurite outgrowth, cellular morphogenesis and synaptic function.

摘要

脑岛皮质(IC)的大小和活动异常,该脑区与幻听和语言有关,先前在精神分裂症的脑成像研究中已被发现。此外,在精神分裂症患者的许多脑区中,第2层皮质已被证明存在异常。在本研究中,二维差异凝胶电泳(2-D DIGE)被用于定量分析在显微切割的IC组织第2层中精神分裂症患者和对照病例(每组n = 15)的蛋白质表达。蛋白质组学分析显示,精神分裂症患者中有57个蛋白质斑点存在显著差异表达(p<0.05)。随后使用蛋白质免疫印迹法证实了其中两种差异表达蛋白质的差异表达。这项工作为精神分裂症患者IC第2层中蛋白质表达异常提供了证据,支持了先前关于该皮质层中神经元大小减小的研究。在本研究中异常表达的蛋白质中,超过一半在先前调查精神分裂症或神经退行性疾病的蛋白质组学研究中未曾报道。发现异常表达的蛋白质似乎通过在神经突生长、细胞形态发生和突触功能中的作用共同影响神经元可塑性。

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