R13 elicits TrkB and downstream signaling activation in 5XFAD mice. (A) R13 activates TrkB signaling cascade in the hippocampus of 5XFAD mice in a dose-dependent manner. R13 was dissolved in pure DMSO, then suspended in 0.5% methylcellulose at final concentration of 5% DMSO/0.5% methylcellulose. The suspension was orally administrated to 2 mo old 5XFAD mice (7.25, 21.8 or 43.6 mg/kg/d) consecutively for 3 mo, and the brain lysates were prepared. The p-TrkB and its downstream signals were monitored by immunoblotting, and the ratio of p-TrkB/TrkB, p-Akt/Akt and p-ERK/ERK were quantitatively analyzed. Data are shown as mean ± SEM. *P < 0.01. (B) IHC staining of p-TrkB in 5XFAD brain sections. Here 2-mo-old 5XFAD mice were fed with R13 or vehicle consecutively for 3 mo. The phosphorylation of TrkB in dentate gyrus was detected by IHC with anti–p-TrkB 816 antibodies. (Scale bar: 50 μm.) Quantification of p-TrkB+ neurons in the dentate gyrus. Note that R13 treatment elicited the phosphorylation of TrkB in 5XFAD mice. Data are shown as mean ± SEM. *P < 0.01.