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Title: 胶质细胞与神经元可塑性的关系
Author: 杨云雷
Degree Level: 博士
Issued Date: 2003
Degree Grantor: 中国科学院上海生命科学学院神经科学研究所
Place of Degree Grantor: 中国科学院上海生命科学学院神经科学研究所
Supervisor: 段树民
Keyword: 星状胶质细胞 ; D-丝氨酸 ; 长时程增强(LTP)
Alternative Title: Astrocyte-derived D-serine contributes to hippocampal long-term potentiation
Abstract: 大量的实验证据表明胶质细胞在神经元的功能中起着重要的作用,但是胶质细胞在神经可塑性中的作用还不清楚。我们研究发现星状胶质细胞在长时程增强(LTPi)中起着关键性的作用。我们用突触前和突触后神经元多次关联激活的办法在混和培养的海马神经元上(神经元生长在一层星状胶质细胞上,Mixed cultures)能够诱导出(LTP),而同样方法在培养的纯的海马神经元上(神经元生长在glia conditioned medi。中,而不与星状胶质细胞直接接触,GcM ctlltures)诱导不出LTP。在G C M c ultures中,外加NMDA受体上甘氨酸位点的激动剂,D-丝氨酸(10μM),用关联协同的方法在GCM cultures上能够诱导出LTP。APV(NMDA受体的拮抗剂);DCKA(NMDA受体上的甘氨酸位点的拮抗剂,以及D-氨基酸氧化酶(D-aminp acid oxidose,DAAO,分解内源性D-丝氨酸的酶),都能够阻断mixed cultures和海马脑片上LTP的产生。已知在中枢神经系统中,D-丝氨酸的分布与NMDA受体的分布是非常相似的。在本研究中得知星状胶质细胞通过提供细胞外易化NMDA受体激活的D-丝氨酸的浓度,在长时程增强中起着关键性的作用。通过化学发光法实验,我们得知在mixed cultures media中和纯的星状胶质细胞media中,D-丝氨酸的浓度远远高于纯的神经元media中的D-丝氨酸浓度。同时我们发现在急性分离的海马组织中的突触小体中几乎检测不到D-丝氨酸,而在GPV(glial plosmalemmol vesicles)中D-丝氨酸的含量很高。通过以上实验我们得知,D-丝氨酸主要存在于星状胶质细胞中,并且细胞外的D-丝氨酸主要是由星状胶质细胞分泌的并对突触可塑性起重要的作用
English Abstract: Glial cells have been found to play active roles in multiple neuronal functions, but it is not clear how they may contribute to neuronal plasticity. Here we report that repetitive correlated activation of pre- and postsynaptic neurons induced long-term potentiation (LTP) of synaptic transmission among hippocampal neurons grown on a layer of astrocytes (mixed cultures), but not among neurons cultured in glial conditioned medium (GCM). Supplement of D-serine, an agonist for the glycine binding site of NMDA receptors, enhanced the NMDA receptor activation and enabled the LTP induction in GCM cultures. The induction of LTP in both mixed cultures and hippocampal slices was prevented by NMDA receptor antagonists, glycine binding site blockers of NMDA receptors, or enzyme that degrades endogenous D-serine. By providing extracellular D-serine that facilitates activation of NMDA receptors, astrocytes may thus play a key role in long-term synaptic plasticity. We found that D-serine concentration in either mixed cultures media or pure astrocytes media was higher than that in pure-neuronal cultures, and the D-serine concentration in acutely isolated hippocampal synaptosome was much higher than that in GPV(glial plasmalemmal vesicles). From the above experiments, we concluded that D-serine mainly exists in astrocytes and extracellular D-serine is also mainly secreted from astrocytes, which plays critical roles in neural plasticity.
Language: 中文
Content Type: 学位论文
URI: http://ir.sibs.ac.cn/handle/331001/2255
Appears in Collections:神经所(总)_学位论文

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Recommended Citation:
胶质细胞与神经元可塑性的关系.杨云雷[d].中国科学院上海生命科学学院神经科学研究所,2003.20-25
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