title: Cerebral pyruvate carboxylase flux is unaltered during bicuculline-seizures.
abstract: Glutamine synthesis in the astroglia reflects the sum of neurotransmitter cycling (glutamate and gamma-aminobutyric acid [GABA]) and de novo synthesis (anaplerosis), the latter catalyzed by pyruvate carboxylase. Previous studies have shown that the glutamate plus GABA cycling flux is correlated strongly with neuronal activity; however, the relationship between pyruvate carboxylase flux and neuronal activity is not known. In this study, pyruvate carboxylase flux was assessed during intravenous infusion of [2-(13)C]glucose using localized (1)H-[(13)C] NMR spectroscopy at 7 Tesla in vivo in halothane-anesthetized and ventilated adult Wistar rats during 85 min of bicuculline-induced seizures (1 mg/kg, intravenously) and in nontreated controls. During seizures, concentrations of lactate, alanine, glutamine, GABA, and succinate increased whereas glutamate and aspartate decreased such that the decrease in glutamate plus aspartate equaled the increase in glutamine plus GABA. Pyruvate carboxylase flux was assessed by the sum of [2-(13)C] and [3-(13)C] of glutamine and glutamate (Glx(2+3)) labeling during [2-(13)C]glucose infusion. During seizures the initial rate of Glx(2+3) synthesis (0.069 +/- 0.013 micromol/g/min) was not significantly different (P = 0.68) from that of the controls (0.059 +/- 0.010 micromol/g/min), indicating that anaplerotic flow through pyruvate carboxylase was unaltered. Intense neuronal activation of seizures did not seem to increase anaplerosis through pyruvate carboxylase, despite the substantial increase in neuronal activity and glutamate/glutamine cycling shown in a previous study (Patel et al., 2004b).
authors.affiliation: Department of Diagnostic Radiology and Magnetic Resonance Research Center, Yale University School of Medicine, PO Box 208043, 300 Cedar Street, New Haven, CT 06520, USA. anant.patel@yale.edu
authors.forename: Anant B
authors.initials: AB
authors.lastname: Patel
authors.forename: Golam M I
authors.initials: GM
authors.lastname: Chowdhury
authors.forename: Robin A
authors.initials: RA
authors.lastname: de Graaf
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Rothman
authors.forename: Robert G
authors.initials: RG
authors.lastname: Shulman
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Behar
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001640:Bicuculline; D001923:Brain Chemistry; D002247:Carbon Isotopes / Q000378:metabolism; D002458:Cell Fractionation / Q000379:methods; D002462:Cell Membrane / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D002952:Citric Acid Cycle / Q000502:physiology; D004569:Electroencephalography / Q000379:methods; D005947:Glucose / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D011336:Probability; D011766:Pyruvate Carboxylase / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D019802:Succinic Acid / Q000378:metabolism; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000596:Amino Acids; D002247:Carbon Isotopes; D005680:gamma-Aminobutyric Acid; D019802:Succinic Acid; D011766:Pyruvate Carboxylase; D005947:Glucose; D001640:Bicuculline