Thiamine deficiency encephalopathy in the developing rat

The body and brain growth of the offspring of rats fed a low-thiamine diet from the 14th day of pregnancy was drastically impaired and characteristic neurological signs appeared by 25 days of age. The normal developmental increase in brain transketolase activity, a thiamine-dependent enzyme of the pentose phosphate pathway, occured between 5 and approximately 18 days of age. During this same interval, enzyme activity of the thiamine deficient group declined markedly and by 25 days of age enzyme values were depressed by 73% compared to controls. The pair-fed control offspring, which were markedly undernourished as a result of the anorexia accompanying dietary thiamine deficiency, showed an essentially normal developmental increase in transketolase activity. Of the brain regions, which included those particularly sensitive to thiamine deprivation, transketolase activity was depleted by 85% in the cerebellum, 77% in the brain stem and 68% in the diencephalon of the deficient offspring. In contrast to the developing young, the deficient mothers remained asymptomatic and brain transketolase activity declined by only 20% even after 5 weeks on a low-thiamine diet. Changes in cerebral nucleic acid were a result of undernutrition. The relationship of the altered transketolase activity to the neurological disorder is discussed.