Journal
JOURNAL OF NEUROSCIENCE RESEARCH
Volume 79, Issue 1-2, Pages 128-138Publisher
WILEY-LISS
DOI: 10.1002/jnr.20311
Keywords
anaplerosis; glutamate-glutamine cycle; neuronal-glial trafficking; NMR; [2-C-13]glucose
Categories
Funding
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK027121] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS034813] Funding Source: NIH RePORTER
- NIDDK NIH HHS [R01 DK 27121, R01 DK027121] Funding Source: Medline
- NINDS NIH HHS [R01 NS 34813, R01 NS034813] Funding Source: Medline
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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-C-13]glucose using localized H-1 -[C-13] NMR spectroscopy at 7 Tesla in vivo in halothaneanesthetized 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-C-13] and [3-C-13] of glutamine and glutamate (GlX(2+3)) labeling during [2-C-13]glucose infusion. During seizures the initial rate of GlX(2+3) synthesis (0.069 +/- 0.013 mumol/ g/min) was not significantly different (P = 0.68) from that of the controls (0.059 +/- 0.010 mumol/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). (C) 2004 Wiley-Liss, Inc.
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