Reversible impairment of cerebral DNA synthesis in thiamine deficiency

The effect of thiamine deficiency on rat brain DNA and RNA synthesis was investigated. Thiamine deficiency, culminating in encephalopathy (symptomatic stage) was induced by dietary thiamine deprivation of 4 to 5 weeks. The encephalopathy could be completely reversed within 6 hours by parenteral administration of thiamine. Controls consisted of pair-fed and ad libitum-fed littermates given the same diet supplemented with thiamine. Brain DNA and RNA synthesis was determined by administration of labeled thymidine, orotic acid, or adenine into the cerebral ventricle and measuring the incorporation of the appropriate labeled precursor into DNA or RNA. Thiamine deficiency (symptomatic stage) had no effect on net DNA and RNA level in any brain area studied. Also, no consistent alteration of brain RNA synthesis was shown in severe thiamine deficiency. By contrast, DNA synthesis in symptomatic thiamine-deficient rats was reduced to 22, 37, 31, and 19 per cent, respectively, of pair-fed control values in the cortex, brain stem, cerebellum, and subcortical structures (p < 0.05). The degree of depressed DNA synthesis increased with the extent and duration of thiamine deprivation. Following reversal of the encephalopathy with parenteral thiamine, DNA synthesis in all brain areas increased markedly to and above control values. These data indicate that the thiamine deficiency state interferes with the synthesis of some discrete DNA pool(s) in the brain. This effect may be due to thiamine deficiency per se and/or some thiamine-induced impaired food assimilation or utilization.