Lentz Margaret R, Lee Vallent, Westmoreland Susan V, Ratai Eva-Maria, Halpern Elkan F, González R Gilberto
Department of Neuroradiology/A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA 02129, USA.
NMR Biomed. 2008 Oct;21(8):878-87. doi: 10.1002/nbm.1276.
MRS has often been used to study metabolic processes in the HIV-infected brain. However, it remains unclear how changes in individual metabolites are related to one another in this context of virus-induced central nervous system dysfunction. We used factor analysis (FA) to identify patterns of metabolite distributions from an MRS study of healthy macaques and those infected with simian immunodeficiency virus (SIV) which were moribund with AIDS. FA summarized the correlations from nine metabolites into three main factors. Factor 3 identified patterns that discern healthy animals from those with SIV/AIDS. Factor 2 was able to differentiate between animals that had encephalitis and those moribund with AIDS but lacking encephalitis. Specifically, Factor 2 was able to distinguish animals with moderate to severe encephalitis from animals with mild or no encephalitis as well as uninfected controls. FA not only confirmed the involvement of neuronal metabolites (N-acetylaspartate and glutamate) in disease severity, but also detected changes in creatine and myo-inositol that have not been observed in the SIV macaque model previously. These results suggest that the divergent pathways of N-acetylaspartate and creatine in this disease may enable the commonly reported ratio N-acetylaspartate/creatine to be a more sensitive marker of disease severity.
磁共振波谱(MRS)常被用于研究HIV感染大脑中的代谢过程。然而,在病毒诱导的中枢神经系统功能障碍的背景下,个体代谢物的变化如何相互关联仍不清楚。我们使用因子分析(FA)从健康猕猴以及患有艾滋病濒死的感染猿猴免疫缺陷病毒(SIV)的猕猴的MRS研究中识别代谢物分布模式。FA将九种代谢物之间的相关性总结为三个主要因子。因子3识别出能区分健康动物和患有SIV/艾滋病动物的模式。因子2能够区分患有脑炎的动物和患有艾滋病濒死但无脑炎的动物。具体而言,因子2能够将患有中度至重度脑炎的动物与患有轻度或无脑炎的动物以及未感染的对照区分开来。FA不仅证实了神经元代谢物(N-乙酰天门冬氨酸和谷氨酸)与疾病严重程度有关,还检测到了肌酸和肌醇的变化,这些变化在之前的SIV猕猴模型中未被观察到。这些结果表明,在这种疾病中,N-乙酰天门冬氨酸和肌酸的不同变化途径可能使常用的N-乙酰天门冬氨酸/肌酸比值成为疾病严重程度更敏感的标志物。