ISCHEMIA INDUCED NEUROGENESIS AND PLASTICITY

描述(摘自摘要)：新的细胞在整个成人的大脑中诞生 生活。新生细胞的一个来源是齿状回的颗粒下带。 海马体的。新生细胞具有形成神经元的潜力， 星形胶质细胞或少突胶质细胞。许多细胞出生在颗粒下层， 成熟神经元迁移到颗粒细胞层。NMDA受体， 癫痫发作和应激激素调节这种神经发生。我们发现， 缺血也会上调神经发生。采用BrdU免疫组织化学方法 显示1-2周齿状颗粒下层细胞新生增加9倍 在全脑缺血后。颗粒下层的新生细胞迁移 进入颗粒细胞层，60%-66%成熟为神经元。其中一些细胞 出生在颗粒下层的婴儿也迁移到齿状门部，在那里10%-20% 变成星形胶质细胞。脑缺血诱导的齿状神经再生不是由 由内嗅皮层细胞死亡引起的应激。这项研究的目的是 研究新生神经元的命运，并研究其机制 啮齿类动物脑内神经发生的缺血诱导。据推测， 全脑缺血后出生在齿状体内的神经元：将轴突延伸到 靶向CA3锥体神经元；上调突触蛋白；增加 CA3区锥体神经元上的突触数目增加； 齿状颗粒细胞层的神经元。实验将决定：是否 逆行转运染料注入海马区CA3区 BrdU标记核与NeuN、MAP-2和Calbindin神经元的共定位 全脑缺血后齿状回颗粒细胞层的标志物； 新生儿全脑缺血后突触前蛋白表达上调 神经元和海马区CA3区；苔藓纤维数量 缺血后CA3区锥体神经元上的突触增多； 全脑缺血后颗粒细胞神经元总数发生变化。它是 还假设在脑缺血后促红细胞生成素在神经胶质细胞中被诱导。 海马体被释放并作用于齿状体内的促红细胞生成素受体 祖细胞启动祖细胞的增殖和 神经再生增加。实验将确定：促红细胞生成素 和/或促红细胞生成素受体在海马区增加 脑缺血；脑室注射促红细胞生成素是否增加神经发生 以及脑室注射抗体是否 促红细胞生成素和/或促红细胞生成素受体减弱神经发生 在全脑缺血后。这些研究对于理解 海马区缺血性损伤后功能恢复的机制。

DESCRIPTION (From Abstract): New cells are born in the brain throughout adult life. One source of newborn cells is the subgranular zone of the dentate gyrus of the hippocampus. The newborn cells have the potential for forming neurons, astrocytes or oligodendrocytes. Many cells born in the subgranular zone that migrate into the granule cell layer form mature neurons. NMDA receptors, seizures and stress hormones regulate this neurogenesis. We have found that ischemia also up-regulates neurogenesis. BrdU immunohistochemistry was used to show a 9-fold increase of cell birth in the dentate subgranular zone 1-2 weeks following global ischemia. The newborn cells in the subgranular zone migrate into the granule cell layer where 60-66% mature into neurons. Some of the cells born in the subgranular zone also migrate into the dentate hilus where 10-20% become astrocytes. The ischemia-induced dentate neurogenesis was not caused by stress of by cell death in entorhinal cortex. The present study is designed to examine the fate of the newborn neurons and to examine the mechanism of ischemic induction of neurogenesis in the rodent brain. It is hypothesized that the neurons born in the dentate following global ischemia: extend axons to the target CA3 pyramidal neurons; up-regulate synaptic proteins; increase the numbers of synapses on CA3 pyramidal neurons; and increase the total number of neurons in the dentate granule cell layer. Experiments will determine: whether retrogradely transported dyes injected into the CA3 zone of hippocampus co-localize with BrdU labeled nuclei and the NeuN, MAP-2 and calbindin neuronal markers in the dentate granule cell layer following global ischemia; Whether pre-synaptic proteins are up-regulated following global ischemia in the newborn neurons and in the CA3 zone of hippocampus; whether the number of mossy fiber synapses on CA3 pyramidal neurons increases following ischemia; and whether the total number of granule cell neurons changes following global ischemia. It is also hypothesized that erythropoetin is induced in glial cells in the ischemic hippocampus, is released and acts on erythropoetin receptors on dentate progenitor cells to initiate proliferation of the progenitor cells and increased neurogenesis. Experiments will determine whether: erythropoetin and/or erythropoetin receptors are increased in hippocampus following global ischemia; whether ventricular infusion of erythropoetin increases neurogenesis from dentate progenitor cells; and whether ventricular infusion of antibodies to erythropoetin and/or erythropoetin receptors attenuate neurogenesis following global ischemia. These studies are important for understanding the mechanism of recovery of function following ischemic injury to the hippocampus.