Cerebral glutamate metabolism in Parkinson's disease: an in vivo dynamic 13C NMS study in the rat

The aim of this work was to explore in vivo the metabolism of the basal ganglia in a rat model of Parkinson's disease. 13C NMR spectroscopy was used to monitor the synthesis of glutamate/glutamine from [2-13C] sodium acetate. 13C label incorporation in glutamate at the carbon C4 was measured in the brain of rats in different physiopathological states and after antiparkinsonian treatment. Studies were performed in control rats (n = 6) and parkinsonian rats (n = 5) in a stable state and after acute levodopa administration (50 mg/kg iv). 13C NMR spectra recorded using a 1H/13C surface probe were acquired in the injured cerebral hemisphere. The sequence was a 13C acquisition sequence with 1H-decoupling during acquisition, which lasted 17 min, six spectra were obtained during the acetate infusion. Levels of glutamate C4 expressed as a percentage of the lipid resonance that appears in the same spectrum were significantly higher in parkinsonian rats than in controls after 34 min (45.1 ± 12.8% vs. 32.0 ± 3.7%; P < 0.05), 51 min (49.0 ± 5.6% vs. 29.8 ± 4.0%; P < 0.001), 68 min (61.6 ± 12.5% vs. 43.5 ± 13.7%; P < 0.01), and 85 min (46.8 ± 5.8% vs. 27.4 ± 7.4%; P < 0.05) of substrate infusion. In parkinsonian rats receiving an acute levodopa injection, the relative proportion of glutamate C4 was statistically lower than in parkinsonian rats receiving saline. Our results show that the metabolism of neuronal glutamate increases in dopamine-depleted striatum and that is restored by administration of levodopa.