EFFECT OF THIAMINE DEPRIVATION AND THIAMINE ANTAGONISTS ON THE LEVEL OF γ‐AMINOBUTYRIC ACID AND ON 2‐OXOGLUTARATE METABOLISM IN RAT BRAIN12

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Abstract
Brain levels of y‐aminobutyric acid (GABA), glutamate and 2‐oxoglutarate, activities of glutamate decarboxylase GABA‐transaminase plus succinic semiaidehyde dehydrogenase and blood levels of glutamate and 2‐oxoglutarate were determined in normal, thiamine‐deprived, oxythiamine‐treated and pyrithiamine‐treated rats. Brain GABA levels were significantly reduced in thiamine‐deprived and pyrithiamine‐treated rats, but the activities of the enzymes of the GABA shunt pathway were not affected. Brain levels of glutamate were decreased and of 2‐oxoglutarate increased in all three types of deficiency. This was associated with similar decreases in glutamate and increases in 2‐oxoglutarate in the blood in all three deficient groups. Intraventricular injections of 2‐[U‐14C] oxoglutarate into the brain in these four groups of rats resulted in some significant differences in distribution of 14C in various TCA‐pathway intermediates and satellite compounds in the brain. Increases in 14C‐label were observed for glutamine and 2‐oxoglutarate in all three deficient groups as compared to controls. The 14C content of succinate, fumarate and aspartate was decreased in the thiamine deprived and PTh‐treated groups and [14C]glutamate was decreased in all three deficient groups. The 14C content of GABA was not significantly affected.

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