Article: article from journal or magazin.
Metabolic changes in quinolinic acid-lesioned rat striatum detected non-invasively by in vivo (1)H NMR spectroscopy.
Journal of Neuroscience Research
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.Publication Status: ppublish
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.
Amino Acids/metabolism, Animals, Cell Death/drug effects, Cell Death/physiology, Disease Models, Animal, Dose-Response Relationship, Drug, Energy Metabolism/drug effects, Energy Metabolism/physiology, Female, Glucose/metabolism, Huntington Disease/chemically induced, Huntington Disease/metabolism, Magnetic Resonance Spectroscopy/instrumentation, Magnetic Resonance Spectroscopy/methods, Mitochondria/drug effects, Mitochondria/metabolism, Neostriatum/drug effects, Neostriatum/metabolism, Neuroglia/drug effects, Neuroglia/metabolism, Neurons/drug effects, Neurons/metabolism, Neurotoxins/pharmacology, Oxidative Stress/drug effects, Oxidative Stress/physiology, Phosphocreatine/metabolism, Quinolinic Acid/pharmacology, Rats, Rats, Inbred F344
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