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.
Chateil
J
J
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
Biran
M
M
Thiaudière
E
E
Canioni
P
P
Merle
M
M
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