ADULT-ONSET HYPOTHYROIDISM AND THE CEREBRAL METABOLISM OF (1,2-C-13(2)) ACETATE AS DETECTED BY C-13 NUCLEAR-MAGNETIC-RESONANCE

The effects of adult-onset hypothyroidism on the metabolic compartment ation of the cerebral tricarboxylic acid cycle and the gamma-aminobuty ric acid (GABA) shunt have been investigated by C-13 nuclear magnetic resonance spectroscopy. Rats thyroidectomized as adults and age-matche d controls were infused in the right jugular vein with unlabeled or (1 ,2-C-13(2)) acetate solutions for 60 min. At the end of the infusion, the brains were frozen in situ and perchloric acid extracts were prepa red and analyzed by C-13 nuclear magnetic resonance and reverse-phase HPLC. Thyroidectomized animals showed a decrease in the incorporation of C-13 from (1,2-C-13(2)) acetate in cerebral metabolites and an incr ease in the concentrations of unlabeled glutamate and GABA. Computer-a ssisted interpretation of the C-13 multiplets observed for the carbons of glutamate, glutamine, and GABA indicated that adult onset hypothyr oidism produced 1) a decrease in the contribution of infused (1,2-C-13 (2)) acetate to the glial tricarboxylic acid cycle; 2) an increase in the contribution of unlabeled acetyl-CoA to the neuronal tricarboxylic acid cycle; and 3) impairments in the exchange of glutamate, glutamin e, and GABA between the neuronal and glial compartments. Despite the f act that the adult brain has often been considered metabolically unres ponsive to thyroid hormone status, present results show metabolic alte rations in the neuronal and glial compartments that are reversible wit h substitution therapy.