EXPRESSION OF RECEPTOR PHOSPHATASES IN THE BRAIN

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The long term objective of this project is to determine the role of the novel receptor-protein tyrosine phosphatases in the development and function of the brain. Because phosphorylation and dephosphorylation are intrinsically linked processes, it is expected that the function of the receptors with tyrosine phosphatase activity will be linked to that of growth factors with tyrosine kinase activity. These factors are important for development, plasticity and nerve regeneration. Moreover, preliminary studies indicate that the receptor phosphatases are a) highly expressed during neural development, b) they are enriched in the adult hippocampal formation, an area that retains plasticity and is involved in the pathogenesis of some mental diseases. Thus, the specific aims of this project are: (1) to test the hypothesis that the expression of the receptor-protein tyrosine phosphatases in the brain is developmentally regulated; (2) to map the brain distribution of these novel receptors; (3) to examine their expression in the rat hippocampal formation, during sprouting, regeneration and reactive gliosis that will be produced by entorhinal cortex lesions and adrenalectomy; and (4) to test in vitro the hypothesis that the expression of the receptor phosphatases in neural cell lines is determined by agents that affect their differentiation and development. The project requires the use of quantitative in situ hybridization techniques, Northern blot analysis and immunocytochemical techniques to determine the regional and cellular expression of the different receptor phosphatases in the rat brain. The proposed research has implications for mental health because the receptor tyrosine phosphatases are highly concentrated in the brain cortex and in the hippocampal formation. These structures are involved in memory and learning, and are affected in AIzheimer's disease, normal aging, schizophrenia and certain forms of epilepsy.