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

多营养因子（PTN）是一种新型的神经营养因子，分子量为18 kDa，具有肝素结合能力。在新生儿髓鞘形成期间，PTN在大脑中的表达达到最高水平。为了研究PTN在中枢神经系统（CNS）中负责髓鞘形成的细胞类型少突胶质细胞（OL）的增殖和分化中的生物学作用，将新生大鼠全脑胶质细胞原代培养在含溴脱氧尿苷（BrdU）的无血清化学定义培养基中培养72 h。细胞增殖标志物和一组神经营养因子和胶质营养因子，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)，浓度分别为50 ng/ml，以及它们的组合，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细胞数量增加3倍，而暴露于bFGF和/或PDGF后，A2B5^+BrdU^+ OL祖细胞数量增加5倍。igf - 1或bFGF + PDGF可诱导01^+BrdU^-成熟OL的数量增加3倍，这是一个非常小的群体，而PTN则没有。这些结果表明，PTN是中枢神经系统髓鞘形成过程中诱导OL成熟的重要因子。

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.