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

Intrastriatal injection of quinolinic acid (QA) provides an animal model of Huntington disease. In vivo H-1 NMR spectroscopy was used to measure the n eurochemical profile non-invasively in seven animals 5 days after unilatera l injection of 150 nmol of QA. Concentration changes of 16 metabolites were measured from 22 mul volume at 9.4 T. The increase of glutamine ((+25 +/- 14)%, mean +/- SD, n = 7) and decrease of glutamate (-12 +/- 5)%, N-acetyla spartate (-17 +/- 6)%, taurine (-14 +/- 6)% and total creatine (-9 +/- 3%) were discernible in each individual animal (P < 0.005, paired t-test). Meta bolite concentrations in control striata were in excellent agreement with b iochemical literature. The change in glutamate plus glutamine was not signi ficant, implying a shift in the glutamate-glutamine interconversion, consis tent with a metabolic defect at the level of neuronal-glial metabolic traff icking. The most significant indicator of the lesion, however, were the cha nges in glutathione ((-19 +/- 9)%, (P < 0.002)), consistent with oxidative stress. From a comparison with biochemical literature we conclude that high -resolution in vivo H-1 NMR spectroscopy accurately reflects the neurochemi cal changes induced by a relatively modest dose of QA, which permits one to longitudinally follow mitochondrial function, oxidative stress and glial-n euronal metabolic trafficking as well as the effects of treatment in this m odel of Huntington disease. (C) 2001 Wiley-Liss, Inc.