Figure 3.
Effects of systemic 7,8-DHF on BDNF-TrkB signaling 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 hippocampal lysates from wild-type and 5XFAD mice treated with 7,8-DHF or vehicle. (b–d) Immunoreactive bands for phosphorylated TrkB (b), total TrkB (c), and mature BDNF (d) were quantified and expressed as the percentage of vehicle-treated wild-type control levels (n=6–9 mice per group). Note that hippocampal phospho-TrkB levels are dramatically reduced in vehicle-treated 5XFAD mice (*p<0.05 vs wild-type, vehicle), and this reduction is completely rescued by 7,8-DHF treatments (#p<0.05 vs 5XFAD, vehicle). In fact, phospho-TrkB levels in 7,8-DHF-treated 5XFAD mice are significantly higher than those of wild-type vehicle controls (*p<0.05). Moreover, repeated 7,8-DHF treatments also rescues the downregulation of total TrkB protein levels in 5XFAD mice (#p<0.05); however, it shows a trend toward reducing TrkB receptors in wild-type controls (p=0.15). Meanwhile, 7,8-DHF treatments do not affect baseline levels of mature BDNF in the hippocampus of wild-type mice or BDNF reductions in 5XFAD mice. All data are presented as mean±SEM.