Effect of deep pentobarbital anesthesia on neurotransmitter metabolism in vivo: on the correlation of total glucose consumption with glutamatergic action.
The effect of deep barbiturate anesthesia on brain glucose transport, TCA cycle flux, and aspartate, glutamate, and glutamine metabolism was assessed in the rat brain using 13C nuclear magnetic resonance spectroscopy at 9.4 T in conjunction with [1-13C] glucose infusions. Brain glucose concentrations were elevated, consistent with a twofold reduced cerebral metabolic rate for glucose (CMRglc) compared with light alpha-chloralose anesthesia. Using a mathematical model of neurotransmitter metabolism, several metabolic reaction rates were extracted from the rate of label incorporation. Total oxidative glucose metabolism, CMRglc(ox), was 0.33 +/- 0.03 micromol x g(-1) x min(-1). The neuronal TCA cycle rate was similar to that in the glia, 0.35 +/- 0.03 micromol x g(-1) x min(-1) and 0.26 +/- 0.06 micromol x g(-1) x min(-1), respectively, suggesting that neuronal energy metabolism was mainly affected. The rate of pyruvate carboxylation was 0.03 +/- 0.01 micromol x g(-1) x min(-1). The exchange rate between cytosolic glutamate and mitochondrial 2-oxoglutarate, Vx, was equal to the rate of neuronal pyruvate dehydrogenase flux. This indicates that Vx is coupled to CMRglc(ox), implying that the malate-aspartate shuttle is the major mechanism that facilitates label exchange across the inner mitochondrial membrane. The apparent rate of glutamatergic neurotransmission, V(NT), was 0.04 +/- 0.01 micromol x g x min, consistent with strong reductions in electrical activity. However, the rates of cerebral oxidative glucose metabolism and glutamatergic neurotransmission, CMRglc(ox)/V(NT), did not correlate with a 1:1 stoichiometry.
Choi
In-Young
IY
Department of Radiology, University of Minnesota, Center for MR Research, Minneapolis 55455, USA.
Lei
Hongxia
H
Gruetter
Rolf
R
D000768:Anesthesia, General; D000818:Animals; D001921:Brain / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000502:physiology; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010424:Pentobarbital; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology
D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D010424:Pentobarbital; D005947:Glucose