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

N-acetylaspartate (NAA) quantification by H-1-magnetic resonance spectrosco py has been commonly used to assess in vivo neuronal loss in neurodegenerat ive disorders. Here the authors used ex vivo and in vivo H-1-magnetic reson ance spectroscopy in mt and primate models of progressive striatal degenera tion induced by the mitochondrial toxin 3-nitropropionate (3NP) to determin e whether early NAA depletions could also be associated with neuronal dysfu nction. In rats that were treated for 3 days with 3NP and had motor symptom s, the authors found a significant decrease in NAA concentrations, specific ally 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 decre ase in striatal NAA con-centrations was observed in association with the oc currence of dying neurons in the dorsolateral striatum. In 3NP-treated prim ates, a similar striatal-selective and early decrease in NAA concentrations was observed after only a few weeks of neurotoxic treatment, without any s ign of ongoing cell death. This early decrease in striatal NAA was partiall y reversed after 4 weeks of 3NP withdrawal. These results demonstrate that early NAA depletions reflect a reversible state of neuronal dysfunction pre ceding cell degeneration and suggest that in vivo quantification of NAA H-1 -magnetic resonance spectroscopy may become a valuable tool for assessing e arly neuronal dysfunction and the effects of potential neuroprotective ther apies in neurodegenerative disorders.