Poly-L-ornithine blocks the inhibitory effects of fibronectin on oligodendrocyte differentiation and promotes myelin repair  

作　　者：Ya-Jie Xiong Shahid Hussain Soomro Zhong-Hai Huang Pan-Pan Yu Jie Ping Hui Fu 

机构地区：[1]Department of Anatomy,School of Basic Medical Sciences,Wuhan University,Wuhan,Hubei Province,China [2]Guangdong-Hongkong-Macao Institute of CNS Regeneration,Ministry of Education Joint International Research Laboratory of CNS Regeneration,Jinan University,Guangzhou,Guangdong Province,China [3]Department of Pharmacology,School of Basic Medical Sciences,Wuhan University,Wuhan,Hubei Province,China

出　　处：《Neural Regeneration Research》2023年第4期832-839,共8页中国神经再生研究（英文版）

基　　金：supported by the National Nature Science Foundation of China,Nos.81371338(to HF)and 82071369(PPY)。

摘　　要：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.

关 键 词：differentiation Erk1/2 extracellular matrix FIBRONECTIN lysolecithin-induced demyelination OLIGODENDROCYTE PI3K poly-L-ornithine proliferation REMYELINATION 

分 类 号：R741[医药卫生—神经病学与精神病学]