The developing brain depends upon many factors to create appropriate connections between diverse areas in the neuraxis. Glycoconjugates are likely to play a role in cell-cell interactions during brain development due to their cell surface locations and the diversity of their potential recognition structures. A central theme of this project is that spatial restriction of glycoconjugate expression is particularly important for the developing olfactory system. In addition, the olfactory system of rodents is one site where gonadal steroids may play significant roles in modulating physiological functions related to reproduction. We will test the hypothesis that the expression of selected alpha-galactosyl glycoconjugates is spatially restricted in the rat olfactory system. The distribution of specific alpha-galactose containing glycoconjugates will be determined in multiple components of the olfactory system in normal animals and in animals treated with an inhibitor of alpha-galactosidase. We will further test the hypothesis that gonadal steroids modulate selected carbohydrate expression, specifically, alpha-galactosyl containing glycoconjugates, in components of the mammalian olfactory system. We will identify glycoproteins and glycolipids with terminal alpha-galactosyl residues that are qualitatively or quantitatively differentially expressed as a function of sex and age in the rat olfactory system as detected by a novel lectin and antibody blot screening technique. We will then generate monoclonal antibodies against such molecules, followed by isolation and structure determination. An inhibitor of alpha-galactosidase will be utilized again to test the hypothesis that sex or age dependent antigen expression is a function of terminal sugar modulation, Finally, we will use the newly generated monoclonal antibodies to study the distribution, processing and hormone dependence of antigen expression with immunocytochemical and immunoblot methods. The importance of hormone effects is underscored by evidence of sex differences and androgen influences in the susceptibility to certain syndromes, learning disabilities and neurological disorders, and hypotheses that these arise from gonadal influences during critical periods.
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