Effect of vitamin B-6 nutrition on the levels of dopamine, dopamine metabolites, dopa decarboxylase activity, tyrosine, and GABA in the developing rat corpus striatum

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Abstract
Evidence presented in this manuscript indicates that prenatal and postnatal vitamin B-6 undernutrition produces the loss of dopamine (DA) in the corpus striatum of the developing rat brain. The concentration of striatal DA in rats fed vitamin B-6 inadequate diets was significantly lower than rats fed optimal diets at 28 and 56 days of age. The differences in striatal DA concentrations among vitamin B-6 dietary groups was more evident with age. Measurements of the major metabolites of DA, homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) in rat corpus striatum showed a significant decrease in HVA level in B-6 restricted rats compared to B-6 sufficient groups. Striatal DOPAC levels were not significantly different among any of the groups at any age. The activity of dopa decarboxylase holoenzyme was found to be significantly lower in the corpus striatum of rats fed suboptimal B-6 diets. Whether this finding has a significant effect on DA levels has yet to be determined since dopa decarboxylase is not the rate-limiting enzyme in the synthesis of DA. In an effort to determine the underlying mechanism for the loss of striatal DA, the concentration of its precursor tyrosine (TYR) was measured. Vitamin B-6 undernutrition had no significant effect on the levels of TYR in rat corpus striatum. The concentration of the inhibitory neurotransmitter GABA was also measured. The results indicate that as expected the levels of striatal GABA were significantly lower than controls at 14 and 28 days of age. On the other hand, striatal GABA levels in B-6 restricted rats did not differ from controls at 56 days of age. These results indicate that vitamin B-6 undernutrition has different effects on the ontogenesis of DA and GABA in the same brain region. In summary, this study shows that long-term vitamin B-6 undernutrition produces a loss of neurochemical indices of dopaminergic neuron function in the rat corpus striatum. They also suggest that dopaminergic neurons of the nigrostriatal tract may be vulnerable to long-term vitamin B-6 undernutrition.