Metabolism of [1-(13)C)glucose and [2-(13)C]acetate in the hypoxic rat brain..
The effects of hypoxia on the metabolism of the central nervous system were investigated in rats submitted to a low oxygen atmosphere (8% O(2); 92% N(2)). [1-(13)C]glucose and [2-(13)C]acetate were used as substrates, this latter being preferentially metabolized by glial cells. After 1-h substrate infusion, the incorporation of 13C in brain metabolites was determined by NMR spectroscopy. Under hypoxia, an important hyperglycemia was noted. As a consequence, when using labeled glucose, the specific enrichment of brain glucose C1 was lower (48.2+/-5.1%) than under normoxia (66.9+/-2.5%). However, relative to this specific enrichment, the (13)C incorporation in amino acids was increased under hypoxia. This suggested primarily a decreased exchange between blood and brain lactate. The glutamate C2/C4 enrichment ratio was higher under hypoxia (0.62+/-0.01) than normoxia (0.51+/-0.06), indicating a lower glutamate turnover relative to the neuronal TCA cycle activity. The glutamine C2/C4 enrichment ratio was also higher under hypoxia (0.87+/-0.07 instead of 0.65+/-0.11), indicating a new balance in the contributions of different carbon sources at the acetyl-CoA level. When using [2-(13)C]acetate as substrate, no difference in glutamine enrichment appeared under hypoxia, whereas a significant decrease in glutamate, aspartate, alanine and lactate enrichments was noted. This indicated a lower trafficking between astrocytes and neurons and a reduced tricarboxylic acid cycle intermediate recycling of pyruvate.
Résonance Magnétique des Systèmes Biologiques, UMR 5536, Centre National de la Recherche Scientifique, Université Victor Ségalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France. jean-francois.chateil@rmsb.u-bordeaux2.fr
J
J
Chateil
M
M
Biran
E
E
Thiaudière
P
P
Canioni
M
M
Merle
D000085:Acetates / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002247:Carbon Isotopes; D005947:Glucose / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000085:Acetates; D002247:Carbon Isotopes; D005947:Glucose