Portacaval anastomosis results in altered neuron--astrocytic metabolic trafficking of amino acids: evidence from 13C-NMR studies.
13C-NMR spectroscopy was used to evaluate the dynamic consequences of portacaval anastomosis on neuronal and astrocytic metabolism and metabolic trafficking between neurons and astrocytes. Glutamate is predominantly labeled from [1-13C]glucose, whereas [2-13C]acetate is more efficient in labeling glutamine, in accordance with its primary metabolism in astrocytes. Alanine and succinate labeling was only observed with [1-13C]glucose as precursor. Brain [1-13C]glucose metabolism in portacaval-shunted rats was similar to that in sham-operated controls with the exception of labeled glutamine and succinate formation, which was increased in shunted rats. The 13C enrichment was, however, decreased owing to an increase in total glutamine and succinate. Using [2-13C]acetate, on the other hand, flux of astrocytic label to neurons was severely decreased because label incorporation into glutamate, aspartate, and GABA was decreased following portacaval shunting. The latter amino acids are predominantly localized in neurons. These findings demonstrate that metabolic trafficking of amino acids from astrocytes to neurons is impaired in portacaval-shunted rats.
Sonnewald
U
U
MR.Center, SINTEF UNIMED, Trondheim, Norway.
Therrien
G
G
Butterworth
R F
RF
D000085:Acetates / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002247:Carbon Isotopes; D002264:Carboxylic Acids / Q000378:metabolism; D002952:Citric Acid Cycle; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D011167:Portacaval Shunt, Surgical; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000085:Acetates; D000596:Amino Acids; D002247:Carbon Isotopes; D002264:Carboxylic Acids; D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005947:Glucose