EXPRESSION OF RECEPTOR PHOSPHATASES IN THE BRAIN

本项目的长期目标是确定 新的受体蛋白酪氨酸磷酸酶的发展和 大脑的功能。 因为磷酸化和去磷酸化 由于这些进程之间存在着内在联系， 具有酪氨酸磷酸酶活性的受体将与 具有酪氨酸激酶活性的生长因子。这些因素很重要 发育，可塑性和神经再生。此外，初步 研究表明受体磷酸酶a）高度表达 在神经发育过程中，B）它们在成年海马中富集 形成，一个保留可塑性的区域，并参与 某些精神疾病的发病机制。因此，这一具体目标 项目是：（1）测试的假设，表达的 受体蛋白酪氨酸磷酸酶在大脑中是发育 调节;（2）绘制这些新受体的大脑分布;（3） 为了检测它们在大鼠海马结构中的表达， 发芽，再生和反应性胶质增生， 内嗅皮质病变和肾上腺切除术;（4）体外测试 神经细胞中受体磷酸酶的表达 细胞系是由影响其分化的因子决定的， 发展该项目要求使用定量原位 杂交技术、北方印迹分析和免疫细胞化学 技术来确定的区域和细胞表达的 不同的受体磷酸酶。拟议研究 对精神健康有影响，因为受体酪氨酸 磷酸酶高度集中在大脑皮层和大脑皮层中。 海马结构这些结构与记忆有关， 学习，并受到阿尔茨海默病，正常衰老， 精神分裂症和某些形式的癫痫。

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.