The Study On The Function Underlying The Effects Of NKX2.2 In Remyelination

Myelin is an important component of the central nervous system(CNS),which is essential for maintaining the normal function of this system.Destruction and damage of the myelin sheath can lead to a variety of myelin-related diseases,such as multiple sclerosis and amyotrophic lateral sclerosis.Therefore,finding an effective way to promote the repair and regeneration of myelin sheaths is important to the treatment of these disease.In the early CNS development,NKX2.2 is highly expressed in the newly differentiated oligodendrocyte progenitor cells(OPCs).The deletion of this gene causes the delayed differentiation of OPCs,while the overexpression of this gene induces the precocious OL differentiation.In the demyelinated tissue,NKX2.2is expressed in OPCs around or within lesion,inferring the important role of this gene in remyelination.In this study,we established the demyelination model induced by lysophosphatidylcholine(LPC)and cuprizone(CPZ),with the purpose to explore the regulatory function of NKX2.2 in the process of remyelination.The experimental results showed that:(1)The expression of Nkx2.2 met the experimental expectations,and the immunofluorescence results showed that the expression of Nkx2.2 was hardly detected in the conditional knockout mice.However,for Nkx2.2 conditional overexpression mice,the expression level of Nkx2.2 was significantly higher than that of the control group mice.(2)In the chronic demyelinating model of mice induced by CZP,at day 28 after induction,the expression of PLP and PDGFRα in Nkx2.2conditional knockout mice and control mice had no significant difference,and the expression level of PLP in the striatum region of both mice was low;On the 7th day after remyelination,compared with the control group mice,the expression of MBP and PLP in Nkx2.2 conditional knockout mice was significantly reduced,while the expression of PDGFRα was not significantly changed.(3)In the LPC induced acute demyelination model of mice,on the 7th day after induction,compared with the control group mice,the expression of MAG in Nkx2.2 conditional knockout mice was significantly reduced,while the expression of PDGFRα was not significantly different.(4)In the chronic demyelination model induced by CZP in mice,on the 7th day after remyelination,compared with the control group mice,the expression of MBP and PLP in Nkx2.2 conditional overexpression mice was significantly upregulated,while the expression of PDGFRα was not significantly altered.In this study,we conclude that:(1)The deletion of Nkx2.2 gene leads to the inhibition of myelin repair in the central nervous system.(2)The overexpression of Nkx2.2 gene promotes remyelination.Through this study,we hope to discover the mechanism underlying remyelination and provide new clue to the treatment of disease involving in demyelination.