Metabolic changes in quinolinic acid-lesioned rat striatum detected non-invasively by in vivo (1)H NMR spectroscopy.
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.
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Department of Radiology, University of Minnesota, 2021 6th Street SE, Minneapolis, MN 55455, USA.
Keene
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Pfeuffer
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Low
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Gruetter
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D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006816:Huntington Disease / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation / Q000379:methods*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010725:Phosphocreatine / Q000378:metabolism; D017378:Quinolinic Acid / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D000596:Amino Acids; D009498:Neurotoxins; D010725:Phosphocreatine; D017378:Quinolinic Acid; D005947:Glucose