Vitamin B-6 is an essential factor in infant nutrition in that it plays a vital role in the development and normal functioning of the central nervous system. Recent studies have shown that based on biochemical measurements, a state of deficiency or increased requirement exists in pregnant women on self-selected diets. Maternal vitamin B-6 status is known to have a direct effect on the vitamin B-6 content of the milk. Investigators have shown that low levels of maternal B-6 intakes does not maintain milk B-6 levels by mobilization of body stores. Therefore, mothers with low or deficient B-6 intakes prior and during gestation and lactation will affect the B-6 nutritional status of their infants with potential deleterious effects on central nervous system development. An association between maternal B-6 intakes and neurological disabilities of the infant at birth has been suggested by several investigators. Our preliminary studies have shown that marked alterations in the ontogenic development of several neurotransmitter systems occurs as a result of perinatal vitamin B-6 deprivation and that these effects occur more rapidly than previously known. The proposed study will investigate the effect of maternal vitamin B-6 nutrition during gestation and lactation on the neurochemical and behavioral development of the offspring. The use of various levels of maternal B-6 intake will make possible the study of functional relationships between B-6 levels and its neurochemical effects at different ages. These measures will be correlated with biochemical indicators of B-6 nutritional status in maternal blood. Furthermore, we propose studies to determine the role of 3-hydroxykynurenine in epileptic seizures associated with vitamin B-6 deficient neonatal rats.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD020939-03
Application #
3319442
Study Section
Human Development and Aging Subcommittee 1 (HUD)
Project Start
1986-07-01
Project End
1989-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Public Health
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Waymire, K G; Mahuren, J D; Jaje, J M et al. (1995) Mice lacking tissue non-specific alkaline phosphatase die from seizures due to defective metabolism of vitamin B-6. Nat Genet 11:45-51
Guilarte, T R (1993) Vitamin B6 and cognitive development: recent research findings from human and animal studies. Nutr Rev 51:193-8
Pilachowski, J; Guilarte, T R (1993) Postnatal development and GABA allosteric modulation of benzodiazepine receptor binding in the vitamin B-6 deficient rat brain. Neurochem Res 18:1249-54
Guilarte, T R; Eastman, C L (1993) Is 3-hydroxykynurenine an endogenous neurotoxin in Huntington's disease? J Neurol Sci 116:227-8
Eastman, C L; Guilarte, T R; Lever, J R (1992) Uptake of 3-hydroxykynurenine measured in rat brain slices and in a neuronal cell line. Brain Res 584:110-6
Guilarte, T R (1991) Reduced NMDA receptor-ion channel function in the vitamin B-6 restricted neonatal rat brain. Neurosci Lett 121:207-10
Guilarte, T R (1991) Abnormal endogenous amino acid release in brain slices from vitamin B-6 restricted neonatal rats. Neurosci Lett 121:203-6
Eastman, C L; Guilarte, T R (1990) The role of hydrogen peroxide in the in vitro cytotoxicity of 3-hydroxykynurenine. Neurochem Res 15:1101-7
Guilarte, T R (1989) 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. Neurochem Res 14:571-8
Guilarte, T R (1989) Regional changes in the concentrations of glutamate, glycine, taurine, and GABA in the vitamin B-6 deficient developing rat brain: association with neonatal seizures. Neurochem Res 14:889-97

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