脑源性神经营养因子对胚鼠大脑皮质神经元发挥保护作用的细胞内信号传导机制
发布时间：2019-01-28 19:07
【摘要】：大量研究表明缺氧是造成神经元死亡的重要原因之一，宫内缺氧可致胎儿宫内窘迫而损伤脑细胞，造成生长发育迟缓，同时因累及神经系统发育中的多个区域而遗留永久性的损伤，成活者常遗留脑瘫、智力低下等严重后遗症。脑源性神经营养因子(brain-derived neurotrophic factor，BDNF)作为脑组织中含量最丰富的神经营养因子，，在中枢神经系统内合成并广泛存在于脑组织，包括大脑皮层、海马、基底前脑、纹状体、下丘脑和小脑，其中以海马和皮层中含量最高。BDNF通过其特异性受体酪氨酸激酶(TrkB)参与细胞的分化、粘着、增殖与成熟等重要的生物学过程。目前已有大量研究表明，在脑外伤、低血糖、脑缺血、脑缺氧及抽搐损伤时，细胞内BDNF其受体TrkB的表达均受到明显影响，加入外源性BDNF可有效减轻神经元所受损伤。 我们前期已用多种试验方法证明了BDNF对缺氧胚鼠脑皮质神经元有确切保护作用，但BDNF与TrKB结合后将胞外刺激信号传递入核内的机制尚未完全明确。BDNF细胞内信号传递途径主要有两条，即丝裂原活化蛋白激酶(Mitogen-activated protein kinase，MAPK)信号通路和磷酯酰肌醇3激酶(phosphatidylinositol-3-kinase，PI-3-K)／AKT信号通路。在
[Abstract]:A large number of studies have shown that hypoxia is one of the important causes of neuron death. Intrauterine hypoxia can cause fetal distress and damage brain cells, resulting in growth retardation. At the same time, permanent damage is left over from multiple areas of nervous system development. Survivors often leave serious sequelae such as cerebral palsy, mental retardation and so on. As the most abundant neurotrophic factor in brain tissue, brain-derived neurotrophic factor (brain-derived neurotrophic factor,BDNF) is synthesized and widely distributed in the central nervous system, including cerebral cortex, hippocampus, basal forebrain and striatum. The hypothalamus and cerebellum have the highest content in hippocampus and cortex. BDNF participates in the important biological processes of cell differentiation adhesion proliferation and maturation through its specific receptor tyrosine kinase (TrkB). A large number of studies have shown that the expression of BDNF receptor TrkB in brain injury, hypoglycemia, cerebral ischemia, cerebral anoxia and convulsion injury is significantly affected. Exogenous BDNF can effectively alleviate the neuronal injury. We have demonstrated the protective effect of BDNF on cerebral cortical neurons in anoxic embryos by several experimental methods. However, the mechanism of extracellular stimulation signal transduction into nucleus after BDNF and TrKB binding is not completely clear. There are two main signal transduction pathways in BDNF cells, that is, mitogen-activated protein kinase (Mitogen-activated protein kinase,). MAPK signaling pathway and phosphoryl inositol 3 kinase (phosphatidylinositol-3-kinase,PI-3-K) / AKT signaling pathway. In
【学位授予单位】：四川大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R363
本文编号：2417225
[Abstract]:A large number of studies have shown that hypoxia is one of the important causes of neuron death. Intrauterine hypoxia can cause fetal distress and damage brain cells, resulting in growth retardation. At the same time, permanent damage is left over from multiple areas of nervous system development. Survivors often leave serious sequelae such as cerebral palsy, mental retardation and so on. As the most abundant neurotrophic factor in brain tissue, brain-derived neurotrophic factor (brain-derived neurotrophic factor,BDNF) is synthesized and widely distributed in the central nervous system, including cerebral cortex, hippocampus, basal forebrain and striatum. The hypothalamus and cerebellum have the highest content in hippocampus and cortex. BDNF participates in the important biological processes of cell differentiation adhesion proliferation and maturation through its specific receptor tyrosine kinase (TrkB). A large number of studies have shown that the expression of BDNF receptor TrkB in brain injury, hypoglycemia, cerebral ischemia, cerebral anoxia and convulsion injury is significantly affected. Exogenous BDNF can effectively alleviate the neuronal injury. We have demonstrated the protective effect of BDNF on cerebral cortical neurons in anoxic embryos by several experimental methods. However, the mechanism of extracellular stimulation signal transduction into nucleus after BDNF and TrKB binding is not completely clear. There are two main signal transduction pathways in BDNF cells, that is, mitogen-activated protein kinase (Mitogen-activated protein kinase,). MAPK signaling pathway and phosphoryl inositol 3 kinase (phosphatidylinositol-3-kinase,PI-3-K) / AKT signaling pathway. In
【学位授予单位】：四川大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R363
【引证文献】
相关硕士学位论文 前1条
1 刘书红;盐酸美金刚对血管性痴呆大鼠CREB和细胞色素C表达的影响[D];郑州大学;2010年
本文编号：2417225
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