关键词: 细胞外基质, 纤连蛋白, 多聚鸟氨酸, 少突胶质细胞, 增殖, 分化, 细胞外调节蛋白激酶1/2, PI3K, 溶血卵磷脂, 脱髓鞘, 髓鞘再生

Abstract: The extracellular matrix surrounding oligodendrocytes plays an important role during myelination and remyelination in the brain. In many cases, the microenvironment surrounding demyelination lesions contains inhibitory molecules, which lead to repair failure. Accordingly, blocking the activity of these inhibitory factors in the extracellular matrix should lead to more successful remyelination. In the central nervous system, oligodendrocytes form the myelin sheath. We performed primary cell culture and found that a natural increase in fibronectin promoted the proliferation of oligodendrocyte progenitors during the initial stage of remyelination while inhibiting oligodendrocyte differentiation. Poly-L-ornithine blocked these inhibitory effects without compromising fibronectin’s pro-proliferation function. Experiments showed that poly-L-ornithine activated the Erk1/2 signaling pathway that is necessary in the early stages of differentiation, as well as PI3K signaling pathways that are needed in the mid-late stages. When poly-L-ornithine was tested in a lysolecithin-induced animal model of focal demyelination, it enhanced myelin regeneration and promoted motor function recovery. These findings suggest that poly-L-ornithine has the potential to be a treatment option for clinical myelin sheath injury.

Key words: differentiation, Erk1/2, extracellular matrix, fibronectin, lysolecithin-induced demyelination, oligodendrocyte, PI3K, poly-L-ornithine, proliferation, remyelination