Cerebral glutamate metabolism in Parkinson's disease: an in vivo dynamic (13)C 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. (13)C NMR spectroscopy was used to monitor the synthesis of glutamate/glutamine from [2-(13)C] sodium acetate. (13)C 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). (13)C NMR spectra recorded using a (1)H/(13)C surface probe were acquired in the injured cerebral hemisphere. The sequence was a (13)C acquisition sequence with (1)H-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.
Chassain
Carine
C
INSERM EMI 9904, Faculté de Médecine et de Pharmacie, 28 place Henri Dunant, 63001 Clermont-Ferrand, France. kchassin@sancy.clermont.intra.fr
Bielicki
Guy
G
Donnat
Jean-Pierre
JP
Renou
Jean-Pierre
JP
Eschalier
Alain
A
Durif
Franck
F
D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001479:Basal Ganglia / Q000378:metabolism*; D002247:Carbon Isotopes; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018698:Glutamic Acid / Q000096:biosynthesis / Q000378:metabolism*; D005972:Glutaminase / Q000378:metabolism; D005973:Glutamine / Q000096:biosynthesis / Q000378:metabolism; D007262:Infusions, Intravenous; D007980:Levodopa / Q000627:therapeutic use; D050356:Lipid Metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017072:Neostriatum / Q000378:metabolism; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019346:Sodium Acetate / Q000378:metabolism* / Q000493:pharmacokinetics
D000978:Antiparkinson Agents; D002247:Carbon Isotopes; D005973:Glutamine; D018698:Glutamic Acid; D019346:Sodium Acetate; D007980:Levodopa; D016627:Oxidopamine; D005972:Glutaminase; D004298:Dopamine