Mdivi-1,An Inhibitor Of Mitochondrial Fission,has Neuroprotective Effect On EAE Mice

Objective:In this study,Mitochondrial division inhibitor 1(Mdivi-1)was applied to treat experimental autoimmune encephalomyelitis(EAE)in mice to investigate its neuroprotective effect.The EAE mice were induced by myelin oligodendrocyte glycoprotein peptides(myelin oligodendrocyte glycoprotein peptides-35~55,MOG35~55),and the clinical and pathological changes as well as the protective effects on the central nervous system were observed in each group of EAE mice.To explore the therapeutic effect of Mdivi-1 on EAE and its possible mechanism,providing a new theoretical and experimental basis for clinical treatment of multiple sclerosis.Methods:30 female C57 BL / 6 mice EAE model was established.It is randomly divided into mdivi-1 treatment group(Mdivi-1 treatment group)and DMSO control group(EAE control group).Mdivi-1 was dissolved in 0.1% DMSO,15 in each group,and intraperitoneal injection of Mdivi-1 was performed on the third day after immunization.Animals were killed on the 28 th day after immunization.LFB myelin staining and immunofluorescence histochemical staining of CNPase,NF-M,map-2,Synaptophysin,NeuN,GDNF,CNTF,BDNF,NGF were performed on the frozen sections of the spinal cord.The obtained experimental data were statistically analyzed using Graphpad Prism5.0 software.Results:1.Compared with DMSO control group,Mdivi-1 treatment group can reduce the EAE clinical score,reduce the EAE cumulative clinical score and reduce the EAE maximum clinical score(p<0.05,p<0.01).2.Compared with the DMSO control group,LFB staining and immunostaining of CNPase in the Mdivi-1 treatment group showed a reduced myelin loss area,suggesting that Mdivi-1 has a protective and repair effect on EAE myelin injury(p<0.01).3.Compared with DMSO control group,Mdivi-1 increased the immunofluorescence intensity of NF-M MAP-2,Synaptophysin labeled in spinal cord white matter,indicating that mdivi-1 protected the integrity of axons(p<0.01).4.Compared with DMSO control group,Mdivi-1 increased the number of NeuN-labeled neurons,indicating that Mdivi-1 has a protective effect on neurons(p<0.01).5.Compared with DMSO control group,Mdivi-1 increased the immunofluorescence intensity of GDNF,CNTF,BDNF and GDNF labeled in spinal cord white matter,indicating that Mdivi-1 promoted the expression of neurotrophic factor(p<0.01).Conclusion:In this study,we analyzed the effect of Mdivi-1 on neuroprotection.The results show that Mdivi-1 effectively improved EAE severity by reducing the demyelination.Moreover,Mdivi-1-treated mice showed a more intense MAP-2,synaptophysin and NF-M positive signal in the CNS.Mdivi-1 increased the number of positive cells labeled by NeuN in the gray matter of spinal cord.In addition,Mdivi-1 promoted the expression of GDNF,CNTF,BDNF and NGF in spinal cord.These findings demonstrate that Mdivi-1 has neuroprotective effect on EAE mice.