The Experimental Study Of APOE Mimetic Peptide COG1410 Regulating The Phenotypic Conversion Of Astrocyte Through Up-Regulating LRP1

Objective In our previous study,the results showed that APOE mimetic peptide COG1410 could improve the cognitive function of APP/PS1 transgenic mice,and found the change of astrocyte phenotype.We will further explore whether peptide COG1410 can change the phenotype of astrocytes in vitro,and explore the possible mechanism of mediating the phenotypic conversion of astrocyte.Method In vivo: Western blot and immunofluorescence techniques are used to detect the expression of LRP1 in tissue samples.In vitro: primary astrocyte culture,CCK8 method is used to detect the survival rate of astrocytes treated with different concentrations of peptide COG1410,and establish the appropriate concentration range of peptide COG1410 intervention.Neuroinflammatory astroglia model(A1 astroglia)was induced by microglia conditioned medium(MCM)prepared by LPS activated microglia.The level of phenotypic marker proteins(C3 and S100A10)of astrocytes and the expression of LRP1 were detected by Western blot and immunofluorescence techniques under the intervention of peptide COG1410.Furthermore,the LRP1 receptor antagonist RAP was added to verify whether LRP1 signal pathway mediated the phenotypic conversion of astrocytes.Results A1 astrocyte was induced by MCM with high expression of C3.COG1410 pretreatment showed the decreased expression of C3 and the increased expression of S100A10(P<0.05),indicating COG1410 inhibits the production of A1 astrocytes and promotes the conversion of astrocytes to A2 type.We found LRP1 was declined in astrocyte treated with MCM,while COG1410 pretreatment appeared to increase the LRP1 expression(P<0.001).And LRP1 antagonist RAP offsets the effect of COG1410 on astrocyte.In addition,the expression of LRP1 was also decreased in APP/PS1double-transgenic mouse model,and was increased after COG1410 treatment.Conclusion Our study shows that APOE mimetic peptide COG1410 inhibits the production of A1 astrocytes and promotes the conversion of astrocytes to A2 type,and the possible mechanism is mediated by LRP1.