Effect Of1,25（OH）₂D₃on Expression Of Transporters And Receptors Mediate Aβ Across The Blood-Brain Barrier

Objectives:To study the effect of1,25(OH)2D3on expression of the transporters and receptors which mediate β-amyloid peptide across the blood-brain barrier. Methods:Thirty six male KM mice (36.8±2.6g) were equally divided into two groups by completely random design. The1,25(OH)2D3administration group were injected with1,25(OH)2D32.5μg/kg/day intraperitoneally every other day, lasting for14days.On the15th day, the control group were intraperitoneally administrated with dissolvent(corn oil) accordingly. Six mice of each group were randomly selected to observe the colocalization of transporters/receptors and brain microvascular endothelial cells using double-labeled immunofluorescence; another6mice were randomly selected to quantitate the expression of transporters and receptors on brain microvascular endothelial cells by immunohistochemistry; the rest6mice were to detect Vitamin D receptor levels using Western blot. Results:The expression of Aβ transporters and receptors on brain microvascular endothelial cells is apparently visible; The optical density in the hippocampal microvascular endothelial cells for P-gp in control group and VD group are577.9±165.8and981.6±148.3, respectively; There were significant difference on P-gp expression between the two groups(P <0.05). The optical density in the hippocampal microvascular endothelial cells for LRP1in control group and VD group are134.2±34.2and875.5±184.9, respectively; There were significant difference on LRP1expression between the two groups(P<0.05). The optical density in the hippocampal microvascular endothelial cells for RAGE in control group and VD group are684.8±171.4and1662.2±202.1,respectively; There were significant difference on RAGE expression between the two groups(P<0.001). The relative grey levels of Vitamin D receptor in hippocampus for control group and VD group are0.305±0.025and0.447±0.027, repectively; There were significant difference on VDR levels between the two groups(P<0.001). Conclusions:1,25(OH)2D3can induce the expression of Aβ efflux transporter/receptor P-gp and LRP1,as well as influx receptor RAGE expression, which may via the vitamin D receptor.