This application will study the effect of dietary level of vitamin B6 on neurochemical changes which occur during pregnancy in the mouse. During pregnancy 1) mice ar more susceptible to seizures than are non-pregnant controls; 2) there are decreased concentrations of the neurotransmitters norepinephrine and gamma-aminobutyric acid in brain; 3) there is an increase n brain levels of the tryptophan metabolite 3-hydroxykynurenine, which is known to induce seizures; and 4) they have decreased levels of the coenzyme form of vitamin B6 in plasma, liver, and possibly brain. It is our hypothesis that the vitamin B6 deficiency is responsible for the altered concentrations of neurotransmitters and increased levels of kynurenines in brain. We suggest that these alterations may be involved in the increased susceptibility to seizures during pregnancy. One serious complication of pregnancy in human is preeclampsia/eclampsia, which is characterized by edema, proteinuria, hypertension, and spontaneous, life threatening seizures. In these individuals the deficit in plasma vitamin B6 is greater than in normal pregnancies. The deficiency of vitamin B6 cannot be corrected with ordinary dietary supplementation of vitamin B6, indicating that some biochemical or physiological mechanism is involved. We believe that the mouse can be used as a model to study this condition. We propose to study the effects of vitamin B6 nutriture on brain neurochemistry in pregnancy by adjusting the dietary level of pyridoxine. Two strains of mice which differ in susceptibility to pregnancy-induced seizures will be used to study the relationship between vitamin B6 nutritional status and neurochemical adjustments which occur during pregnancy.
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