【作者】 陈建芳；

【导师】 姚忠祥；

【作者基本信息】 第三军医大学 ， 人体解剖与组织胚胎学， 2006， 硕士

【摘要】 神经干细胞(Neural stem cells, NSCs)是指中枢神经系统(Central nervous system, CNS)存在的具有自我更新自我增殖能力和多种分化潜能的特殊细胞群。NSCs广泛存在于哺乳动物的中枢神经系统,其中侧脑室附近的室管膜前下区(Anterior subventricular zone, SVZa)被认为是哺乳动物神经系统中NSCs最为集中的部位之一。研究发现SVZa的神经干细胞产生后,逐渐向嗅球(Olfactory bulb, OB)迁移,在从SVZa迁移到OB的过程中形成一条高度局限的迁移通道――喙侧迁移流(Rostral migratory stream, RMS),位于迁移流中的神经干细胞保持增殖状态和神经干细胞特征而不进一步分化,在迁移到嗅球后才进一步分化成熟。SVZa神经干细胞的增殖、分化以及在喙侧迁移流通道迁移的过程中,不但受到遗传因素的影响,而且受到多种细胞因子(环境因素)的调控作用。细胞因子是一类由细胞分泌的调节细胞生长、增殖及分化的多肽小分子,对中枢神经系统中的各种生物效应具有广泛多样的调节作用。细胞因子通过其受体和受体介导的细胞因子信号转导途径发挥生物学效应。CNS中研究较多的细胞因子有生长激素(Grouth hormone, GH)、促红细胞生成素(erythropoietin, EPO)、胰岛素(insulin)、IGF-1 (insulin-like growth factor)等等。细胞因子的效应又受多种因子的调节,包括SOCS家族。SOCS (suppressors of cytokine signaling,细胞因子信号抑制因子)是近年来发现的一类可被多种细胞因子诱导产生,对细胞因子信号通路具有负反馈调节作用的蛋白分子,参与多种细胞因子、生长因子和激素的信号调节。SOCS蛋白最初被认为是JAK/STAT信号通路的负调节因子,受多种细胞因子诱导表达并对这些因子有负反馈调节作用。SOCS家族有CIS和SOCS1-7共8个成员,分别在不同的组织表达并被不同的细胞因子诱导,调控不同的JAK/STAT途径。SOCS2是SOCS家族的成员之一,研究发现,SOCS2 mRNA在动物胚胎和成年的许多组织都有表达,且在发育和成年的动物神经系统中均有表达。最初发现SOCS2是GH信号的负性调节因子,后来发现胰岛素与SOCS2也有密切关系。最新研究表明SOCS2是一种潜在的神经分化调控因子,能促进NSC向神经元而非胶质细胞方向分化,对神经元的功能具有重要作用,但其作用机制不更多还原

【Abstract】 Neural stem cells (NSCs) exist widely in the mammalian central nervous system and posses the capability of self-renewing, self-duplication, and the potentiality of differentiating into various neural cells. It is believed that the anterior subventricular zone (SVZa) which neighbouring the Lateral ventricle (LV) is one of the main areas where NSCs localized. The SVZa NSCs migrate continuously from SVZa to olfactory bulb (OB) and form a highly limited migratory pathway which is called rostral migratory stream (RMS). The SVZa NSCs can keep proliferation and progenitor states all along the RMS and no further differentiation can be seen until arriving at OB. The proliferation, migration and differentiation of SVZa NSCs are regulated not only by hereditary factor but also by kinds of cytokines (environmental factor).Cytokines are secreted polypeptides that take part in the regulation of cell growth, differentiation and proliferation through their receptors and receptor mediating cytokine signal transduction pathways and have multiple effects on the biological processes of CNS. Among them, growth hormone (GH), erythropoietin (EPO), insulin and IGF-1(insulin-like growth factor) have been studied more in CNS. The effects of cytokines are also regulated by various factors mainly by the suppressor of cytokine signaling (SOCS) family. SOCS proteins discovered recently can be induced by a wide range of cytokines including growth factors and hormone. They work as negative feedback regulators of cytokine signal pathways. SOCS proteins were primarily known as negative regulators of Janus-activated kinase (JAK) / signal transducers and activators of transcription (STAT) signaling pathway. There are eight known members of the SOCS gene family (CIS and SOCS1-7) which are expressed in different tissues and induced by different groups of cytokines and regulate different JAK/STAT pathways. As a member of SOCS family, researchers show that SOCS2 mRNA is expressed in many tissues of embryonic and adult animals, especially in nervous system. SOCS2 was primarily known as a negative regulator of GH signaling which was found closely associated with insulin later. Recent studies showed that SOCS2更多还原