Decreased TCA cycle rate in the rat brain after acute 3-NP treatment measured by in vivo 1H-{13C} NMR spectroscopy

Pierre Gilles Henry, Vincent Lebon, Françoise Vaufrey, Emmanuel Brouillet, Philippe Hantraye, Gilles Bloch

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Abstract

Inhibition of succinate dehydrogenase (SDH) by the mitochondrial toxin 3-nitropropionic acid (3-NP) has gained acceptance as an animal model of Huntington's disease. In this study 13C NMR spectroscopy was used to measure the tricarboxylic acid (TCA) cycle rate in the rat brain after 3-NP treatment. The time course of both glutamate C4 and C3 13C labelling was monitored in vivo during an infusion of [1-13C] glucose. Data were fitted by a mathematical model to yield the TCA cycle rate (Vtca) and the exchange rate between α-ketoglutarate and glutamate (Vx). 3-NP treatment induced a 18% decrease in Vtca from 0.71 ± 0.02 μmol/g/min in the control group to 0.58 ± 0.02 μmol/g/min in the 3-NP group (p < 0.001). Vx increased from 0.88 ± 0.08 μmol/g/min in the control group to 1.33 ± 0.24 μmol/g/min in the 3-NP group (p < 0.07). Fitting the C4 glutamate time course alone under the assumption that Vx is much higher than Vtca yielded Vtca = 0.43 μmol/g/min in both groups. These results suggest that both Vtca and Vx are altered during 3-NP treatment, and that both glutamate C4 and C3 labelling time courses are necessary to obtain a reliable measurement of Vtca.

Original languageEnglish (US)
Pages (from-to)857-866
Number of pages10
JournalJournal of Neurochemistry
Volume82
Issue number4
DOIs
StatePublished - Aug 2002

Keywords

  • 3-nitropropionic acid
  • Brain
  • C NMR spectroscopy
  • Glutamate
  • Rat
  • TCA cycle

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