title: Metabolic changes in quinolinic acid-lesioned rat striatum detected non-invasively by in vivo (1)H NMR spectroscopy.
abstract: 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.
authors.affiliation: Department of Radiology, University of Minnesota, 2021 6th Street SE, Minneapolis, MN 55455, USA.
authors.forename: I
authors.initials: I
authors.lastname: Tkác
authors.forename: C D
authors.initials: CD
authors.lastname: Keene
authors.forename: J
authors.initials: J
authors.lastname: Pfeuffer
authors.forename: W C
authors.initials: WC
authors.lastname: Low
authors.forename: R
authors.initials: R
authors.lastname: Gruetter
mesh_terms: 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
chemical_list: D000596:Amino Acids; D009498:Neurotoxins; D010725:Phosphocreatine; D017378:Quinolinic Acid; D005947:Glucose