SummaryThe effect of niacin deficiency on the activities of tyrosine hydroxylase and tryptophan-5-monooxygenase was studied in relation to the contents of catecholamines and serotonin in brain to clarify the role of the vitamin in brain function. Male rats 4 weeks of age were fed a niacin-free, low-protein diet for 3 weeks. Tests for the avoidance learn ing behavior were started at 14 th day in experimental period and were repeated 3 times every other day. After sacrifice on the 21st day, the activities of tyrosine hydroxylase and tryptophan-5-monooxygenase in the brain homogenates were assayed. In the other experiments, contents of dopamine, norepinephrine and serotonin in brain were determined in rats fed on the same niacin-deficient, low-protein diet for 3 weeks. The activity of crude tyrosine hydroxylase in brain was found to be increased significantly in niacin deficiency and was reduced below that of the control one week after niacin supplementation to the deficient rats. On the contrary, contents of dopamine and norepinephrine in whole brain of the niacin-deficient rats showed a significant decrease. No significant dif ference in brain tryptophan-5-monooxygenase activities was observed among niacin-deficient, low-protein control and normal commercial diet groups. Brain serotonin contents of the niacin-deficient animals were almost the same as that of the low-protein control, but were less than that of the rats fed on niacin-supplemented 20% casein diet. Though, no significant difference was observed between the learning abilities of niacin deficient and control groups, these results suggested that the change of catecholamine and serotonin metabolism in brain was one of the causes for some malfunction of the central nervous system induced by niacin deficiency.Pellagra which has been known as a disease caused by niacin deficiency is characterized by dermatitis, diarrhea and dementia. Though the major role of 159 160 H. SANADA, Y. NAKASHIMA, Y. UTSUKI, and S. KAWADA the niacin derivatives, NAD, NADP and their reduced forms, has been found to perticipate.in a variety of metabolic reactions as cofactors of many kinds of redox enzymes, the disturbance of the central nervous system caused by niacin deficiency has not yet been elucidated. Dopamine, norepinephrine and serotonin are thought to be the synaptic neurotransmitters present mainly in the basal ganglia region of brain and have an important role in the brain function. These cate cholamines and serotonin have been shown to be synthesized from tyrosine and tryptophan, respectively, in neurons by enzymatic hydroxylation for which a pteridine cofactor, pteridine reductase, and NAD (P) H are necessary in vivo. In our previous experiments, ascorbic acid deficiency in guinea pig was recognized to cause a decrease of tyrosine hydroxylase activities in brain or adrenals (1-3) and resulted in the low concentration of catecholamines in the adrenals (3). WURT MAN et al. reported a decreased amount of catecholamines in brain of infant rats fed a low-protein diet during...
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