PROLIFERATION AND DIFFERENTIATION OF OLIGODENDROCYTES IN CULTURE INDUCED BY A NEUROTROPHIC FACTOR PLEIOTROPHIN

神经营养因子多效素诱导的培养物中少突细胞的增殖和分化

• 批准号: 08670715
• 负责人: SATOH Jun-ichi
• 金额: $ 1.28万
• 依托单位: Saga Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670715/
• 关键词: pleiotrophin; oligodendrocytes; オソゴデンドロサイト

Pleiotrophin (PTN) is a novel neurotrophic factor with a molecular weight 18 kDa and a heparin-binding capacity. The expression of PTN is observed at a maximum level in the brain during myelination in the neonatal period. To investigate biological roles of PTN in proliferation and differentiation of oligodendrocytes (OL), a cell type responsible for myelination in the central nervous system (CNS), primary cultures of glial cells isolated from whole brains of the newbom rats were incubated for 72 h in the serum-free chemically-defined medium containing bromodeoxyuridine (BrdU), a marker for identification of cellular proliferation and a panel of neurotrophic and gliotrophic factors that include PTN,insulin-like growth factor I (IGF-I), basic fibroblast growth factor (bFGF), plalelet-derived growth factor-AA (PDGF) at a conentration of 50 ng/ml each, and their combinations, followed by analysis using double-labeling immunocytochemistry. A three-fold increase was induced in the number of O4^+BrdU^- immature OL by treatment with PTN and/or IGF-I,while a five-fold increase was induced in that of A2B5^+BrdU^+ OL progenitor cells after exposure to bFGF and/or PDGF.A three-fold increase was induced in the number of 01^+BrdU^- mature OL that constitute a very small population by treatment with IGF-I or bFGF plus PDGF but not with PTN.These results indicate that PTN is an important factor capable of inducing OL maturation during the CNS myelination.

多效素（PTN）是一种新型神经营养因子，分子量为18 kDa，具有肝素结合能力。在新生儿期髓鞘形成期间，在大脑中观察到 PTN 的表达达到最高水平。为了研究 PTN 在少突胶质细胞 (OL)（一种负责中枢神经系统 (CNS) 髓鞘形成的细胞类型）增殖和分化中的生物学作用，将从新生大鼠全脑分离的神经胶质细胞的原代培养物在含有溴脱氧尿苷 (BrdU)（细胞增殖鉴定标记物）的无血清化学成分确定的培养基中孵育 72 小时 以及一组神经营养和胶质营养因子，包括 PTN、胰岛素样生长因子 I (IGF-I)、碱性成纤维细胞生长因子 (bFGF)、血小板衍生生长因子-AA (PDGF)（每种浓度为 50 ng/ml）及其组合，然后使用双标记免疫细胞化学进行分析。 PTN 和/或 IGF-I 处理可诱导 O4^+BrdU^- 未成熟 OL 的数量增加三倍，而暴露于 bFGF 和/或 PDGF 后，A2B5^+BrdU^+ OL 祖细胞的数量可诱导增加五倍。通过用 IGF-I或bFGF加PDGF但不与PTN一起。这些结果表明PTN是能够在CNS髓鞘形成过程中诱导OL成熟的重要因素。

项目成果

Satoh J et al: "Retinoic acid-induced neuronal differentiation regulates expression of mRNAS for neurotrophins and neurotrophin receptors in a human embryonal carcinoma cell line NTera2" Neuropathology. in press (1997)

Satoh J 等人：“视黄酸诱导的神经元分化调节人胚胎癌细胞系 NTera2 中神经营养蛋白和神经营养蛋白受体 mRNA 的表达”《神经病理学》。

Satoh J et al: "Retinoic acid-induced neuronal differentiation regulates expressicn of mRNAs for neurotrophins and neurotrophin receptors in a human embryonal carcinoma cell line NTera2" Neuropathology. 17. 80-88 (1997)

Satoh J 等人：“视黄酸诱导的神经元分化调节人胚胎癌细胞系 NTera2 中神经营养蛋白和神经营养蛋白受体 mRNA 的表达”《神经病理学》。

Satoh J et al: "Cultured skin fibroblasts isolated from mice devoid of the prion protein gene express major heat shock proteins in response to heat stress" Experimental Neurology. in press. (1998)

Satoh J 等人：“从缺乏朊病毒蛋白基因的小鼠中分离出的培养皮肤成纤维细胞在热应激反应中表达主要的热休克蛋白”实验神经学。

Satoh J et al: "Adult-onset Krabbe disease with homozygous T1853C mutation in the galactocerebrosidase gene.Unusual MRI findings of corticospinal tract demyelination" Neurology. 49. 1392-1399 (1997)

Satoh J 等人：“成人发病的克拉伯病，半乳糖脑苷酶基因中存在纯合 T1853C 突变。皮质脊髓束脱髓鞘的异常 MRI 发现”神经病学。

Satoh J et al: "Retinoic acid-induced neuronal differentiation regulates expression of mRNAs for neurotrophins and neurotrophin receptors in a human embryonal carcinoma cell line NTera2" Neuropathology. 17. 80-88 (1997)

Satoh J 等人：“视黄酸诱导的神经元分化调节人胚胎癌细胞系 NTera2 中神经营养蛋白和神经营养蛋白受体 mRNA 的表达”《神经病理学》。