Results from the first five years of funding have demonstrated conclusively that dietary taurine is essential for normal feline pregnancy and outcome, and that its absence from the diet results in excessive reproductive wastage and a number of neurological abnormalities in surviving offspring. We have documented morphological abnormalities in the cerebellum, visual cortex, dorsal roots/spinal cord, retina and tapetum of such animals. We have shown that females consuming diets containing small, but insufficient, amounts of taurine have marginally improved breeding performance and the offspring have more subtle defects. These extensive observations establish that a dietary content of 0.05% taurine is the minimum consistent with normal feline pregnancy and outcome. We propose to extend our examinations of the offspring to include quantitative morphometric measures of brain cells for all three groups, both at weaning 8 weeks after birth and in newborn animals. This will include a laminar analysis of the number of neurons, astrocytes, oligodendrocytes and microglia in the visual cortex and comparison with a non-visual area of cerebral cortex, the frontal cortex. We plan to extend these measurements to the primary visual relays, the lateral geniculate nucleus and the superior colliculus. The results from these studies will indicate how widespread are the effects of taurine deficiency on brain development. In addition, we propose to use our newly prepared taurine antibody in those same animals to examine intercellular diversity of taurine content within cell types, and its response to dietary limitation of taurine. Thus we will determine, for example, if those cerebellar granule cells which fail to migrate from the external granule cell layer are atypically depleted of taurine. Similar observations will be made on the abnormal cells in the visual cortex. The results of these studies will greatly increase our understanding of the role of taurine in the fundamental processes of development and how individual cells are affected by a nutritional deficiency of taurine. We will use conventional morphological stains, as well as quantitative morphometry and immunostaining, to identify the appearance of abnormalities in utero. Finally, the long-term consequences of taurine deficiency during development on functions such as reproduction as well as on brain structure and biochemistry will be continued. Post-weaning intervention with dietary taurine on these parameters will be attempted.
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