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. 2019 Mar 18;18(3):e12932. doi: 10.1111/acel.12932

Figure 3.

Figure 3

In vivo pharmacological inhibition of cholesterol loss in old mice restores hippocampal insulin sensitivity and insulin‐LTD. (a, b) Oral administration of the Cyp46A1 inhibitor Voriconazole reduces hippocampal PI3K/Akt and downstream effector p70S6K hyperactivation in old mice. (a) Western blot of Phospho‐Serine 473 activating residue on Akt. (b) Western blot of p70S6K Phospho‐Threonine 389. (c, d) Oral treatment with Voriconazole decreases insulin resistance marks in hippocampal samples of old mice. (c) Western blots for IRS‐1 resistance marks Phospho‐Serine 632; (d) Phospho‐Serine 307. (e) Voriconazole treatment reduces the inhibitory phosphorylation on GSK3β. (f) Graphic showing insulin‐LTD induction in old mice slices (n = 7) and old mice slices incubated with Voriconazole (n = 8). Hippocampal slices were incubated with Voriconazole 10 nM for 60 min starting 30 min before insulin stimulus. Black box indicates time of insulin application. Gray box indicates time of Voriconazole application. Representative analogue traces below were collected at the indicated time points. Bar graphs: Numbers inside indicate the number of independent experiments. Data are represented as mean ± SEM. t test for (a, b, c, d, e). One‐way ANOVA with post hoc Bonferroni's test for (F). The asterisks indicate the p values (*p < 0.05)