Tkác I, Keene C D, Pfeuffer J, Low W C, Gruetter R
Department of Radiology, University of Minnesota, 2021 6th Street SE, Minneapolis, MN 55455, USA.
J Neurosci Res. 2001 Dec 1;66(5):891-8. doi: 10.1002/jnr.10112.
Intrastriatal injection of quinolinic acid (QA) provides an animal model of Huntington disease. In vivo (1)H NMR spectroscopy was used to measure the neurochemical profile non-invasively in seven animals 5 days after unilateral injection of 150 nmol of QA. Concentration changes of 16 metabolites were measured from 22 microl volume at 9.4 T. The increase of glutamine ((+25 +/- 14)%, mean +/- SD, n = 7) and decrease of glutamate (-12 +/- 5)%, N-acetylaspartate (-17 +/- 6)%, taurine (-14 +/- 6)% and total creatine (-9 +/- 3%) were discernible in each individual animal (P < 0.005, paired t-test). Metabolite concentrations in control striata were in excellent agreement with biochemical literature. The change in glutamate plus glutamine was not significant, implying a shift in the glutamate-glutamine interconversion, consistent with a metabolic defect at the level of neuronal-glial metabolic trafficking. The most significant indicator of the lesion, however, were the changes in glutathione ((-19 +/- 9)%, P < 0.002)), consistent with oxidative stress. From a comparison with biochemical literature we conclude that high-resolution in vivo (1)H NMR spectroscopy accurately reflects the neurochemical changes induced by a relatively modest dose of QA, which permits one to longitudinally follow mitochondrial function, oxidative stress and glial-neuronal metabolic trafficking as well as the effects of treatment in this model of Huntington disease.
纹状体内注射喹啉酸（QA）可提供亨廷顿病的动物模型。在150 nmol QA单侧注射5天后，使用体内¹H核磁共振波谱法对7只动物的神经化学特征进行了非侵入性测量。在9.4 T下，从22微升体积中测量了16种代谢物的浓度变化。每只动物均可观察到谷氨酰胺增加（（+25±14）%，平均值±标准差，n = 7），谷氨酸减少（-12±5）%、N-乙酰天门冬氨酸减少（-17±6）%、牛磺酸减少（-14±6）%以及总肌酸减少（-9±3%）（P < 0.005，配对t检验）。对照纹状体中的代谢物浓度与生化文献中的数据高度吻合。谷氨酸加谷氨酰胺的变化不显著，这意味着谷氨酸-谷氨酰胺相互转化发生了改变，与神经元-胶质细胞代谢转运水平的代谢缺陷一致。然而，病变的最显著指标是谷胱甘肽的变化（（-19±9）%，P < 0.002），这与氧化应激一致。通过与生化文献进行比较，我们得出结论，高分辨率体内¹H核磁共振波谱法能够准确反映相对适度剂量的QA所诱导的神经化学变化，这使得人们能够在该亨廷顿病模型中纵向追踪线粒体功能、氧化应激以及胶质细胞-神经元代谢转运情况，以及治疗效果。
