Effect Of APOE Isoforms On The Growth Of Neuronal Axons

Objective：To explore the effect of APOE different genotype on axonalgrowth and the related mechanism.Methods：Cortical explants were isolated from wild type mice and1-day-old APOE gene knockout mice，and then primary cultured in vitrowith the treatment of the recombinant human ApoE2、3and4(20μg/ml)respectively for5d, then were named ApoE2group、ApoE3group、ApoE4group. At last, all the cultured cells were divided into five groups，namely，WT group、ApoE (–) group、ApoE2group、ApoE3group、ApoE4group.The average lengt of axons and number of neuritis were determine by thephase-contrast microscope. The fluorescence intensity of axons weredetermine by means of immunofluorescence Staining，and Western blottinganalysis were used to detect the expression of cdc42of each group toobserved the effect of different ApoE proteins on the expression of cdc42.Results：At the first、third、fifth day after cultured，the average axonslength of WT group、ApoE2group、ApoE3group was longer than that inApoE (–) group and ApoE4group(p﹤0.05)，but no significant differencesin axonal length occurred either among WT group、ApoE2group andApoE3group or between ApoE(-) group and ApoE4group. Additional，theaverage neurites number of WT、ApoE2and ApoE3group were more thanthat in the group of ApoE(–) and ApoE4at the fifth day(p﹤0.05). Same，there is no significant differrrence between the group in WT、ApoE2、 ApoE3and group in ApoE(–)、ApoE4. The axonal fluorescence intensity ofWT Group, ApoE2Group and ApoE3Group were higher than that ofApoE(-) Group and ApoE4Group (p﹤0.05), but no significant differencein fluorescence intensity either among WT Group, ApoE2Group andApoE3Group or between ApoE(-) Group and ApoE4Group. Theexpression of cdc42in WT Group, ApoE2Group and ApoE3Group werehigher than that of ApoE(-) Group and ApoE4Group (p＜0.05), and againno significant difference in the expression of cdc42was found eitheramong WT Group, ApoE2Group and ApoE3Group or between ApoE(-)Group and ApoE4Group.Conclusion：The growth of neurons axons is differently affected byApoE isoforms, and the effect of ApoE2and ApoE3on the promote theaxon growth is stronger than that of ApoE4. The effect of ApoE isoformson the expression of tubulinⅢ and cdc42is different too, the expression oftubulinⅢ and cdc42in ApoE2and ApoE3group were higher than that ofApoE4group, which maybe one of the mechanism of effect of ApoEisoforms on the growth of neurons axons.