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精神分裂症患者死后大脑中磷脂代谢物的31P核磁共振波谱分析

31P NMR spectroscopy of phospholipid metabolites in postmortem schizophrenic brain.

作者信息

Komoroski Richard A, Pearce John M, Mrak Robert E

机构信息

Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.

出版信息

Magn Reson Med. 2008 Mar;59(3):469-74. doi: 10.1002/mrm.21516.

DOI:10.1002/mrm.21516
PMID:18306399
Abstract

Evidence has been accumulating that schizophrenia involves abnormalities in the composition and metabolism of cell membrane phospholipids (PLs) in the brain. In vivo 31P MRS has been used to measure the metabolic precursors and degradation products of PL metabolism in schizophrenia. Because in vivo line widths are substantially broader than in solution, only the broad phosphomonoester (PME) and phosphodiester bands, or partly resolved resonances of individual metabolites, are typically measured in vivo in the 31P spectrum. In addition to poor resolution, the relatively low signal-to-noise ratio (SNR) makes precise quantitation difficult. An alternative with substantially better resolution and precision for quantitation is high-resolution NMR spectroscopy of extracts of samples from postmortem brain. Here we determine absolute concentrations of the individual PL metabolites phosphocholine (pc), phosphoethanolamine (pe), glycerophosphocholine (gpc), and glycerophosphoethanolamine in aqueous extracts of tissue from frontal, temporal, and occipital cortex of postmortem brain for schizophrenics, controls, and patients with other mental illnesses (psychiatric controls [PC]) using high-resolution 31P NMR spectroscopy. For the complete groups, which included both males and females, there were no statistically significant differences for schizophrenics vs. controls for any of the four PL metabolites in any of the three brain regions. Trends (0.05 < P < 0.10) were noted for increased gpc in schizophrenia in all three regions. PC differed from both controls and schizophrenics in several measures. When only males were considered, gpc was significantly (P < 0.05) elevated in all three brain regions in schizophrenia.

摘要

越来越多的证据表明,精神分裂症与大脑细胞膜磷脂(PLs)的组成和代谢异常有关。体内31P磁共振波谱已被用于测量精神分裂症中PL代谢的代谢前体和降解产物。由于体内线宽比溶液中的宽得多,在31P谱的体内测量中,通常只测量宽的磷酸单酯(PME)和磷酸二酯带,或个别代谢物的部分分辨共振。除了分辨率差外,相对较低的信噪比(SNR)也使得精确定量变得困难。一种分辨率和定量精度明显更高的替代方法是对死后大脑样本提取物进行高分辨率核磁共振波谱分析。在这里,我们使用高分辨率31P核磁共振波谱法测定了精神分裂症患者、对照组和其他精神疾病患者(精神科对照[PC])死后大脑额叶、颞叶和枕叶皮质组织水提取物中单个PL代谢物磷酸胆碱(pc)、磷酸乙醇胺(pe)、甘油磷酸胆碱(gpc)和甘油磷酸乙醇胺的绝对浓度。对于包括男性和女性的完整组,在三个脑区中的任何一个中,精神分裂症患者与对照组在四种PL代谢物中的任何一种上均无统计学显著差异。在所有三个区域中,精神分裂症患者的gpc均有升高趋势(0.05 < P < 0.10)。PC在几个指标上与对照组和精神分裂症患者均不同。仅考虑男性时,精神分裂症患者在所有三个脑区的gpc均显著升高(P < 0.05)。

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