Metabolic changes in quinolinic acid-lesioned rat striatum detected noninvasively by in vivo ¹H NMR spectroscopy

Intrastriatal injection of quinolinic acid (QA) provides an animal model of Huntington disease. In vivo ¹H 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 μl 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 ¹H 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.