Study On The Role Of GDF11 In Promoting Remyelination

Background:Multiple sclerosis(MS)is an immune-mediated inflammatory demyelinating disease of the central nervous system,whose pathological features are demyelination and inflammation.Now,it is still unclear what trigger MS.However,it is generally believed that the undifferentiation of oligodendrocyte precursor cells(OPCs)into oligodendrocytes(OLs)with myelin-forming ability is one of the leading causes of MS.Therefore,it is a therapeutic potential strategy for MS to explore methods and drugs that promote OPCs differentiation and remyelination to repair damaged myelin and prevent the decline of neurological function.Transforming growth factor 11(GDF11)is a secretory signaling molecule in the TGF? superfamily and an important anti-aging factor.And it has been shown that its family members TGF?-1 and Activin A can promote the differentiation and myelination of OPCs.Therefore,we speculate that GDF11 may also have a similar effect.Aim:To study the effects of GDF11 on myelination and regeneration,and to provide new ideas and new potential drugs for the treatment of MS.Methods:In in vitro experiments,we added GDF11 to OPCs cultured and labeled the number of mature OLs by immunofluorescence technique.For development experiments,we examined OLs and myelin expression by immunofluorescence,RT-PCR,transmission electron microscopy and WB techniques after GDF11 injection into neonatal mice.In the EAE model,we used Kono's scoring method,immunofluorescence,transmission electron microscopy and WB techniques to detect the effects of GDF11 on remyelination.Furthermore,we used Cuprizone model to test whether GDF11 could promote remyelination by EC staining in the corpur callosum of mice.Results: 1.In vitro,GDF11 promotes the differentiation of OPCs into mature oligodendrocyte and enhance the processes of OLs.2.In vivo experiments,GDF11 can promote the differentiation of OPCs into mature OLs and promote myelination.3.In the Experimental Autoimmune Encephalomyelitis(EAE)mouse model,GDF11 has the ability to promote OLs differentiation and remyelination.4.In the Cuprizone mouse model,GDF11 has the ability to promote remyelination.Conclusions:In summary,our study identifies a crucial role of GDF11 in oligodendrocyte differentiation,myelination and remyelination in central nervous system,and suggest that GDF11 may be a potential target for the treatment of demyelinating diseases,such as multiple sclerosis.