F. Chapa et al., ADULT-ONSET HYPOTHYROIDISM AND THE CEREBRAL METABOLISM OF (1,2-C-13(2)) ACETATE AS DETECTED BY C-13 NUCLEAR-MAGNETIC-RESONANCE, Endocrinology, 136(1), 1995, pp. 296-305
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.