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.
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