Metabolic changes in quinolinic acid‐lesioned rat striatum detected non‐invasively by in vivo ¹H 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 l volume at 9.4 T. The increase of glutamine ((ϩ25 Ϯ 14)%, mean Ϯ SD, n ϭ 7) and decrease of glutamate (Ϫ12 Ϯ 5)%, N-acetylaspartate (Ϫ17 Ϯ 6)%, taurine (Ϫ14 Ϯ 6)% and total creatine (Ϫ9 Ϯ 3%) were discernible in each individual animal (P Ͻ 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 ((Ϫ19 Ϯ 9)%, P Ͻ 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.

Simultaneous two-voxel localized 1H-observed 13C-edited spectroscopy for in vivo MRS on rat brain at 9.4T: Application to the investigation of excitotoxic lesions

“…Our 1 H spectra matched those of Tkác et al [41]. They explored the model using 1 H spectroscopy and recorded a similar set of data post injection (after five days).…”

Longitudinal MRI and MRSI characterization of the quinolinic acid rat model for excitotoxicity: peculiar apparent diffusion coefficients and recovery of N‐acetyl aspartate levels

“…The normalized NAA levels were defined as the ratio of NAA ipsi / NAA cl . We did not normalize NAA levels to total-Creatine or total-Choline levels since we could not assume that these metabolites remain constant for 49 days post QA-injection, in light of the recent reports showing changes in these metabolites already 5 days post QA-injection (21).…”

“…The 3-NP model has been widely investigated by MR (12,(14)(15)(16)(17)(18). However, a comprehensive longitudinal MR study has not been performed yet on the QA model, although a few MR studies have shown the evolution of the lesion (19,20) while others have shown NAA levels in a dose response manner in one time-point (21,22). We performed in-vivo multiparametric MRI and MRSI that extended over 49 days to assess the spatial and temporal evolution of the QA neuropathology.…”

Developmental and regional changes in the neurochemical profile of the rat brain determined by in vivo 1H NMR spectroscopy

“…The [Glu]/[Gln] ratio in normal brain is an important parameter, because Glu and Gln metabolism in the brain is closely related to neurotransmission and Glu and Gln cycling between neurons and glia (33, 34). In addition, the decrease in [Glu]/[Gln] ratio from a normal value for a specific brain region and age is assumed to be a marker of a metabolic defect (35, 36).…”