Jiang F, Levison S W, Wood T L
Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, Hershey 17033, USA.
J Neurosci Res. 1999 Aug 15;57(4):447-57.
Ciliary neurotrophic factor (CNTF) is produced and released in response to injury in the central nervous system (CNS). While CNTF initially was characterized as a trophic factor for neurons, more recent evidence supports roles for this factor in survival, proliferation, and maturation of oligodendrocyte lineage cells. Evidence is emerging to support the hypothesis that CNTF's actions may include enhancing other growth and trophic factors. Here we tested the hypothesis that CNTF can induce expression of receptors on oligodendrocytes for factors that are known to promote their generation, maturation, and survival. Specifically, we used an in vivo paradigm to test whether CNTF, when injected stereotactically into forebrain white matter of adult rats, could induce mRNA expression for the insulin-like growth factor (IGF) type I receptor (IGF-IR), fibroblast growth factor (FGF) receptor (FGFR)-1, FGFR3, and platelet-derived growth factor (PDGF) receptor-alpha (PDGFRalpha). We determined that CNTF injection increased expression of IGF-IR and FGFR1 mRNAs in adult white matter to 200-250% of control levels. Cellular analysis indicated that these receptor mRNAs were induced in interfascicular oligodendrocytes. In contrast, CNTF had no effect on levels of FGFR3 and PDGFRalpha mRNAs. These results suggest that CNTF enhances the sensitivity of oligodendrocytes to other mitogens and trophic factors via induction of their receptors.
睫状神经营养因子（CNTF）是在中枢神经系统（CNS）受到损伤时产生并释放的。虽然CNTF最初被表征为神经元的营养因子，但最近的证据支持该因子在少突胶质细胞系细胞的存活、增殖和成熟中发挥作用。越来越多的证据支持这样一种假说，即CNTF的作用可能包括增强其他生长和营养因子。在此，我们测试了这样一种假说，即CNTF可以诱导少突胶质细胞上已知促进其生成、成熟和存活的因子的受体表达。具体而言，我们采用体内实验范式来测试，当将CNTF立体定向注射到成年大鼠的前脑白质中时，是否能诱导胰岛素样生长因子（IGF）I型受体（IGF-IR）、成纤维细胞生长因子（FGF）受体（FGFR）-1、FGFR3和血小板衍生生长因子（PDGF）受体α（PDGFRα）的mRNA表达。我们确定，注射CNTF可使成年白质中IGF-IR和FGFR1 mRNA的表达增加至对照水平的200%-250%。细胞分析表明，这些受体mRNA是在束间少突胶质细胞中被诱导产生的。相比之下，CNTF对FGFR3和PDGFRα mRNA的水平没有影响。这些结果表明，CNTF通过诱导少突胶质细胞的受体，增强了它们对其他有丝分裂原和营养因子的敏感性。
