Figure 5.
Effects of systemic 7,8-DHF on APP processing and Aβ levels in 5XFAD mice. 5XFAD and wild-type control mice at 12–15 months of age received repeated administration of 7,8-DHF or vehicle (once daily for 10 consecutive days), and were killed 2 h after the last injection. (a) Immunoblot analysis of hemibrain lysates from wild-type and 5XFAD mice treated with 7,8-DHF or vehicle. (b, c) Immunoreactive bands for BACE1 (b) and C99 (c) were quantified and expressed as the percentage of vehicle-treated wild-type and 5XFAD levels, respectively (n=6–9 mice per group). Note that BACE1 levels are significantly elevated in vehicle-treated 5XFAD mice (*p<0.05 vs wild-type, vehicle), and this upregulation is suppressed by 7,8-DHF treatments (#p<0.05 vs 5XFAD, vehicle). Moreover, repeated 7,8-DHF treatment also significantly reduces baseline levels of BACE1 in wild-type mice (*p<0.05). Consistent with the BACE1 reduction, C99 levels are significantly lowered by 7,8-DHF treatments in 5XFAD mice (#p<0.05). (d, e) Levels of total Aβ40 (d) and Aβ42 (e) were quantified by sandwich ELISAs of guanidine extracts of hemibrain samples and expressed as the percentage of vehicle-treated 5XFAD levels (n=6–9 mice per group). Repeated 7,8-DHF treatment almost equivalently reduced Aβ40 and Aβ42 levels in 5XFAD mouse brains (#p<0.05 vs 5XFAD, vehicle). All data are presented as mean±SEM.