Early N-acetylaspartate depletion is a marker of neuronal dysfunction in rats and primates chronically treated with the mitochondrial toxin 3- nitropropionic acid

Caroline Dautry, Françoise Vaufrey, Emmanuel Brouillet, Nicolas Bizat, Pierre Gilles Henry, Françoise Condé, Gilles Bloch, Philippe Hantraye

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

Abstract

N-acetylaspartate (NAA) quantification by 1H-magnetic resonance spectroscopy has been commonly used to assess in vivo neuronal loss in neurodegenerative disorders. Here, the authors used ex vivo and in vivo 1H- magnetic resonance spectroscopy in rat and primate models of progressive striatal degeneration induced by the mitochondrial toxin 3-nitropropionate (3NP) to determine whether early NAA depletions could also be associated with neuronal dysfunction. In rats that were treated for 3 days with 3NP and had motor symptoms, the authors found a significant decrease in NAA concentrations, specifically restricted to the striatum. No cell loss or dying cells were found at this stage in these animals. After 5 days of 3NP treatment, a further decrease in striatal NAA concentrations was observed in association with the occurrence of dying neurons in the dorsolateral striatum. In 3NP-treated primates, a similar striatal-selective and early decrease in NAA concentrations was observed after only a few weeks of neurotoxic treatment, without any sign of ongoing cell death. This early decrease in striatal NAA was partially reversed after 4 weeks of 3NP withdrawal. These results demonstrate that early NAA depletions reflect a reversible state of neuronal dysfunction preceding cell degeneration and suggest that in vivo quantification of NAA 1H-magnetic resonance spectroscopy may become a valuable tool for assessing early neuronal dysfunction and the effects of potential neuroprotective therapies in neurodegenerative disorders.

Original languageEnglish (US)
Pages (from-to)789-799
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume20
Issue number5
DOIs
StatePublished - 2000

Keywords

  • 3-Nitropropionic acid
  • H-MRS
  • Huntington disease
  • N-acetylaspartate
  • Neurodegeneration
  • Striatum

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