Albrecht Phillip J, Murtie Joshua C, Ness Jennifer K, Redwine Jeffrey M, Enterline Jonathan R, Armstrong Regina C, Levison Steven W
Department of Neuroscience & Anatomy, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Neurobiol Dis. 2003 Jul;13(2):89-101. doi: 10.1016/s0969-9961(03)00019-6.
Multiple sclerosis is characterized by multiple lesions with selective loss of myelin and oligodendrocytes, leading to deficits of sensation and movement, as well as cognitive disabilities. Consequently, a major research endeavor is to identify strategies to enhance oligodendrocyte regeneration and remyelination. FGF-2 is a potent mitogen for OPCs, and it is induced in astrocytes in animal models of demyelinating diseases in conjunction with successful remyelination. However, the factors responsible for inducing FGF-2 after demyelination in astrocytes are unknown. Here we show that CNTF mRNA and protein increase coincident with spinal cord remyelination in mice recovering from MHV-induced demyelination. We identify CNTF within astrocytes surrounding and within remyelinating lesions, and show that CNTF increases FGF-2 ligand and receptor mRNAs in spinal cord after direct application. Furthermore, we show that CNTF increases FGF-2 mRNA approximately 2.5-fold in cultured mouse spinal cord astrocytes. Altogether, these results strongly implicate CNTF as an important cytokine in demyelinating disease and as an upstream regulator of FGF-2 production in astrocytes during early remyelination.
多发性硬化症的特征是存在多个病变，伴有髓鞘和少突胶质细胞的选择性丢失，导致感觉和运动功能障碍以及认知缺陷。因此，一项主要的研究工作是确定增强少突胶质细胞再生和髓鞘再生的策略。成纤维细胞生长因子-2（FGF-2）是少突胶质前体细胞（OPCs）的一种有效促有丝分裂原，在脱髓鞘疾病的动物模型中，它与成功的髓鞘再生一起在星形胶质细胞中被诱导产生。然而，脱髓鞘后在星形胶质细胞中诱导FGF-2的因素尚不清楚。在这里，我们表明，在从鼠肝炎病毒（MHV）诱导的脱髓鞘中恢复的小鼠中，睫状神经营养因子（CNTF）的mRNA和蛋白随着脊髓髓鞘再生而增加。我们在髓鞘再生病变周围和内部的星形胶质细胞中鉴定出CNTF，并表明直接应用后CNTF可增加脊髓中FGF-2配体和受体的mRNA。此外，我们表明CNTF可使培养的小鼠脊髓星形胶质细胞中的FGF-2 mRNA增加约2.5倍。总之，这些结果强烈表明CNTF是脱髓鞘疾病中的一种重要细胞因子，并且是早期髓鞘再生期间星形胶质细胞中FGF-2产生的上游调节因子。
