Leptin and OX-A regulate Tau phosphorylation thereby modulating GSK3β, activity. (A) Representative immunoblots of pY402-Pyk2/Pyk2, pS47- Akt/Akt, pY216-GSK3β/GSK3β, and pT231-Tau/Tau ratios showing the effect of in vivo 2-AGP and AM095 treatment in the ARC of wt and ob/ob mice. Lanes from blots spliced together in a composite image are separated by a dotted black vertical line. Please note that these OD values are expressed as the ratio between phosphorylated and total protein signals. Data are means ± SEM (n = 3 mice/group). The p values were obtained via two-way ANOVA with Tukey's multiple comparisons test. (B) Representative immunoblots of pY402Pyk2/Pyk2, pS473Akt/Akt, pS9GSK3β/GSK3β, pY216GSK3β/GSK3β and pT231-Tau/Tau ratios showing the effect of in vivo leptin, OX-A and SB treatment in the ARC of wt and ob/ob mice. OD values are expressed as the ratio between phosphorylated and total protein signals. Data represent means ± SEM (n = 3/group). The p values were obtained via two-way ANOVA with Tukey's multiple comparisons test. Each comparison is represented as follows: ∗ = wt vs ob/ob, # = wt vs wt treated, $ = ob/ob vs ob/ob treated. Overall significance is represented as follow: ∗, #, $p < 0.05, ∗∗, ##, $$p < 0.01, ∗∗∗, ###, $$$p < 0.001, ∗∗∗∗, ####, $$$$ p < 0.0001. (C) Representative scheme showing the opposite effect of leptin and 2-AG-derived 2-AGP on GSK3β activity and pT231-Tau production.