Human infants fed low-taurine commercial infant formulas have low plasma and urine taurine concentrations compared to infants fed human milk, which is very rich in taurine. Infants and children fed by taurine-free parenteral nutrition show similarly reduced plasma taurine levels and ophthalmopscopic and electroretinographic abnormalities, all of which normalize when taurine is provided. Recently it was reported that human preterm infants fed formula low in taurine had less mature auditory evoked responses and an increased interval between stimulus and response than similar infants fed formula supplemented with taurine. In developing cats, low-taurine diets lead to retinal photoreceptor degeneration as well as abnormal development of the visual cortex and cerebellum. This project is studying dietary taurine deprivation in rhesus monkeys in order to define its functional, biochemical, and morphological effects in a developing primate. In studies now completed, rhesus infants fed a taurine-free soy protein-based human infant formula from birth had reduced plasma taurine levels similar to those in human infants fed the same formulas. Their visual acuity was below normal during the first 3 postnatal months and they showed degenerative changes in retinal photoreceptors, particularly cones in the foveal region, and abnormalities in the morphology of the visual cortex at 3 and 6 months of age. The proposed studies will continue to examine the progression of these effects in 12 and 24-month-old groups and their reversibility in infants deprived of taurine until 6 months and then supplemented until 12 months. Methods will include: 1. Quantitative morphometry and measurements of synapse formation and dendritic spines in visual cortex and frontal cortex; morphology and ultrastructure of the lateral geniculate nucleus and superior colliculus. 2. Additional measures of visual acuity and contrast sensitivity, behavioral tests of color vision, and foveal electroretinograms. 3. Assessment of effects of taurine deprivation on the auditory system, including brain stem auditory evoked responses. 4. Studies of learning and memory, including tests of visual recognition memory in young infants and, in older animals, reversal learning, delayed alternation and delayed matching-to-sample tests. These studies will better define the extent of the effects of taurine deprivation on sensory systems and neural development, whether the change observed at 3 and 6 months increase progressively with age or spontaneously regress with increasing maturity, and to what extent they are reversed by taurine supplementation. Give the similarity of macaque monkeys to human infants in their nutritional requirements, brain development and visual system structure and function, these studies provide the best available model for assessing the nutritional importance of taurine in human infants.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD018678-09
Application #
2197711
Study Section
Nutrition Study Section (NTN)
Project Start
1984-05-01
Project End
1994-11-30
Budget Start
1992-12-01
Budget End
1994-11-30
Support Year
9
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Institute for Basic Research in Dev Disabil
Department
Type
DUNS #
167205090
City
Staten Island
State
NY
Country
United States
Zip Code
10314
Imaki, H; Neuringer, M; Sturman, J (1996) Long-term effects on retina of rhesus monkeys fed taurine-free human infant formula. Adv Exp Med Biol 403:351-60
Sturman, J A; Chesney, R W (1995) Taurine in pediatric nutrition. Pediatr Clin North Am 42:879-97
Neuringer, M; Palackal, T; Sturman, J A et al. (1994) Effects of postnatal taurine deprivation on visual cortex development in rhesus monkeys through one year of age. Adv Exp Med Biol 359:385-92
Sturman, J A (1993) Taurine in development. Physiol Rev 73:119-47
Palackal, T; Neuringer, M; Sturman, J (1993) Laminar analysis of the number of neurons, astrocytes, oligodendrocytes and microglia in the visual cortex (area 17) of 6- and 12-month-old rhesus monkeys fed a human infant soy-protein formula with or without taurine supplementation from birth. Dev Neurosci 15:54-67
Imaki, H; Jacobson, S G; Kemp, C M et al. (1993) Retinal morphology and visual pigment levels in 6- and 12-month-old rhesus monkeys fed a taurine-free human infant formula. J Neurosci Res 36:290-304
Neuringer, M; Sturman, J A; Imaki, H et al. (1992) Regression of taurine depletion in rhesus monkeys deprived of dietary taurine throughout the first year. Adv Exp Med Biol 315:207-14
Sturman, J A; Messing, J M; Rossi, S S et al. (1991) Tissue taurine content, activity of taurine synthesis enzymes and conjugated bile acid composition of taurine-deprived and taurine-supplemented rhesus monkey infants at 6 and 12 mo of age. J Nutr 121:854-62
Palackal, T; Kujawa, M; Moretz, R et al. (1991) Laminar analysis of the number of neurons, astrocytes, oligodendrocytes and microglia in the visual cortex (area 17) of 3-month-old rhesus monkeys fed a human infant soy-protein formula with or without taurine supplementation from birth. Dev Neurosci 13:20-33
Neuringer, M; Palackal, T; Kujawa, M et al. (1990) Visual cortex development in rhesus monkeys deprived of dietary taurine. Prog Clin Biol Res 351:415-22

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