TRAFFICKING OF AMINO-ACIDS BETWEEN NEURONS AND GLIA IN-VIVO - EFFECTSOF INHIBITION OF GLIAL METABOLISM BY FLUOROACETATE

Glial-neuronal interchange of amino acids was studied by C-13 nuclear magnetic resonance spectroscopy of brain extracts from fluoroacetate-t reated mice that received [1,2-C-13]acetate and [1-C-13]glucose simult aneously. [C-13]Acetate was found to be a specific marker for glial me tabolism even with thr large doses necessary for nuclear magnetic reso nance spectroscopy. Fluoroacetate, 100 mg/kg, blocked the glial, but n ot the neuronal tricarboxylic acid cycles as seen from the C-13 labeli ng of glutamine, glutamate, and gamma-aminobutyric acid. Glutamine, bu t not citrate, was the only glial metabolite that could account for th e transfer of C-13 from glia to neurons. Massive glial uptake of trans mitter glutamate was indicated by the labeling of glutamine from [1-C- 13]glucose in fluoroacetate-treated mice. The C-3/C-4 enrichment ratio , which indicates the degree of cycling of label, was higher in glutam ine than in glutamate in the presence of fluoroacetate, suggesting tha t transmitter glutamate (which was converted to glutamine after releas e) is associated with a tricarboxylic acid cycle that turns more rapid ly than the overall cerebral tricarboxylic acid cycle.