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精神分裂症患者尸检垂体中与代谢、激素和应激相关的分子变化。

Metabolic, hormonal and stress-related molecular changes in post-mortem pituitary glands from schizophrenia subjects.

机构信息

Department of Chemical Engineering and Biotechnology, University of Cambridge , Cambridge , UK.

出版信息

World J Biol Psychiatry. 2013 Sep;14(7):478-89. doi: 10.3109/15622975.2011.601759. Epub 2012 Jan 17.

DOI:10.3109/15622975.2011.601759
PMID:22248022
Abstract

OBJECTIVES

To identify a molecular profile for schizophrenia using post-mortem pituitaries from schizophrenia and control subjects.

METHODS

Molecular profiling analysis of pituitaries from schizophrenia (n = 14) and control (n = 15) subjects was carried out using a combination of liquid chromatography tandem mass spectrometry (LC-MS(E)), multiplex analyte profiling (MAP), two-dimensional difference gel electrophoresis (2D-DIGE) and Western blot analysis.

RESULTS

This led to identification of differentially expressed molecules in schizophrenia patients including hypothalamic-pituitary-adrenal axis-associated constituents such as cortisol, pro-adrenocorticotropic hormone, arginine vasopressin precursor, agouti-related protein, growth hormone, prolactin and secretagogin, as well as molecules associated with lipid transport and metabolism such as apolipoproteins A1, A2, C3 and H. Altered levels of secretagogin in serum from a cohort of living first onset schizophrenia patients were also detected, suggesting disease association and illustrating the potential for translating some components of this molecular profile to serum-based assays.

CONCLUSIONS

Future studies on the molecules identified here may lead to new insights into schizophrenia pathophysiology and pave the way for translation of novel diagnostics for use in a clinical setting.

摘要

目的

利用精神分裂症患者和对照者死后的垂体鉴定精神分裂症的分子特征。

方法

采用液相色谱串联质谱(LC-MS(E))、多重分析物分析(MAP)、二维差异凝胶电泳(2D-DIGE)和 Western blot 分析相结合的方法,对精神分裂症(n = 14)和对照(n = 15)受试者的垂体进行分子谱分析。

结果

这导致鉴定出精神分裂症患者中差异表达的分子,包括下丘脑-垂体-肾上腺轴相关成分,如皮质醇、促肾上腺皮质激素原、精氨酸加压素前体、肥胖相关蛋白、生长激素、催乳素和分泌素,以及与脂质转运和代谢相关的分子,如载脂蛋白 A1、A2、C3 和 H。从一组首发精神分裂症患者的血清中也检测到分泌素水平的改变,提示与疾病相关,并说明了将该分子特征的一些成分转化为基于血清的检测的潜力。

结论

对这里鉴定出的分子的进一步研究可能会深入了解精神分裂症的病理生理学,并为用于临床的新型诊断方法的转化铺平道路。

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