EXPRESSION OF RECEPTOR PHOSPHATASES IN THE BRAIN

大脑中受体磷酸酶的表达

• 批准号: 2250928
• 负责人: JOSE M MUSACCHIO
• 金额: $ 15.48万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2250928
• 关键词: adrenalectomy; brain mapping; cell differentiation; dentate gyrus; developmental genetics; developmental neurobiology; embryo /fetus cell /tissue; experimental brain lesion; gene expression; gliosis; hippocampus; immunocytochemistry; in situ hybridization; laboratory mouse; laboratory rat; nervous system regeneration; neural plasticity; neurogenesis; neuronal guidance; northern blottings; phosphoprotein phosphatase; receptor expression; synaptogenesis; tissue /cell culture; vertebrate embryology

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.

该项目的长期目标是确定 新型受体蛋白酪氨酸磷酸酶的开发和 大脑的功能。 因为磷酸化和去磷酸化是 内在联系的过程，预计的功能 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 用于发育、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）它们在成人海马中丰富 地层，一个保留可塑性并参与 一些精神疾病的发病机制。因此，本次活动的具体目标 项目有： (1) 检验假设 大脑中的受体蛋白酪氨酸磷酸酶在发育过程中 受监管； (2)绘制这些新受体的大脑分布图； (3) 检查它们在大鼠海马结构中的表达， 发芽、再生和反应性神经胶质增生将由 内嗅皮质病变和肾上腺切除术； (4) 体外测试 假设神经细胞中受体磷酸酶的表达 线是由影响其分化的因素决定的 发展。该项目要求采用定量原位 杂交技术、Northern blot 分析和免疫细胞化学 确定区域和细胞表达的技术 大鼠大脑中的不同受体磷酸酶。拟议的研究 对心理健康有影响，因为受体酪氨酸 磷酸酶高度集中在大脑皮层和 海马体的形成。这些结构与记忆有关 学习，并受到艾茨海默病、正常衰老的影响， 精神分裂症和某些形式的癫痫症。