Griffin Julian L, Bollard Mary, Nicholson Jeremy K, Bhakoo Kishore
Biological Chemistry, Biomedical Sciences, Imperial College of Science, Technology and Medicine, Exhibition Road, London SW7 2AZ, UK.
NMR Biomed. 2002 Oct;15(6):375-84. doi: 10.1002/nbm.792.
In the investigations of brain function and pathology in vivo by magnetic resonance spectroscopy (MRS), a decrease in the relative concentration of N-acetyl aspartate (NAA) has been correlated with neuronal cell damage or loss, while a relative increase in the resonance intensity of creatine has been correlated with gliosis. However, neither metabolite is confined strictly to one cell-type. In this study, pattern recognition of spectra derived from high-resolution magic angle spinning (HRMAS) (1)H NMR spectroscopy was used to distinguish three neural cell types; cortical astrocytes, cerebellar neurones and O-2A progenitors. The intact cells contained significant amounts of lipid resonances (-CH(2)CH(3) and -CH(2)CH(2)CH(2)-) in all three cell-types, even when a T(2)-edited Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence was used, selectively attenuating resonances from macromolecules. Creatine was also detected in all three cell types. Principle component analysis (PCA) readily differentiated the NMR spectra, based on the individual metabolic profile derived from the cohort of cell type examined using conventional solvent-suppressed and CPMG pulse sequences. Creatine was not found to contribute to this separation. Moreover, the large lipid content of neuronal cells contributed most to the separation from the other cell types. This suggests that during MRS in vivo, where lipid resonances are commonly 'edited out' by T(2) delays, significant information may be sacrificed concerning relative contribution from individual cell types.
在通过磁共振波谱(MRS)对活体脑功能和病理学进行的研究中,N-乙酰天门冬氨酸(NAA)相对浓度的降低与神经元细胞损伤或损失相关,而肌酸共振强度的相对增加与胶质细胞增生相关。然而,这两种代谢物都并非严格局限于一种细胞类型。在本研究中,利用高分辨率魔角旋转(HRMAS)氢核磁共振波谱得到的谱图进行模式识别,以区分三种神经细胞类型:皮质星形胶质细胞、小脑神经元和少突胶质前体细胞。即使使用了T2编辑的Carr-Purcell-Meiboom-Gill(CPMG)脉冲序列选择性衰减大分子的共振,所有这三种细胞类型的完整细胞中仍含有大量脂质共振(-CH(2)CH(3)和-CH(2)CH(2)CH(2)-)。在所有三种细胞类型中也检测到了肌酸。基于使用传统溶剂抑制和CPMG脉冲序列检测的细胞类型群体得出的个体代谢谱,主成分分析(PCA)很容易区分核磁共振谱。未发现肌酸对这种区分有贡献。此外,神经元细胞中大量的脂质成分对其与其他细胞类型的区分贡献最大。这表明在活体MRS过程中,脂质共振通常会因T2延迟而被“编辑掉”,可能会牺牲有关各个细胞类型相对贡献的重要信息。