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. Author manuscript; available in PMC: 2018 Sep 1.
Published in final edited form as: Neurobiol Aging. 2017 May 19;57:75–83. doi: 10.1016/j.neurobiolaging.2017.05.010

Figure 4. Hippocampal GSK3β inhibition rescues spatial memory in db/db mice.

Figure 4

(A), Top panel shows experimental design for chronic intrahippocampal delivery of TDZD-8, a non-ATP-competitive thiadiazolidinone inhibitor with high selectivity for GSK3β (Martinez et al., 2002). Bottom panel shows representative western blot membrane probed with antibodies against active (pS9) and total GSK3β. (B), Quantification of band intensities revealed that intrahippocampal delivery of TDZD-8 blocked dephosphorylation and activation of GSK3β in db/db mice. (C), Hippocampal GSK3β inhibition normalizes spatial recognition memory in db/db mice, based on increased alternation in the Y-maze. (D), Deficits in novel object exploration time at early post-training intervals in db/db mice were blocked by intrahippocampal TDZD-8. (E), Persistent, GSK3β-mediated reductions in novel object preference were evident at longer retention intervals in db/db mice based on comparison of exploration bout number. For all graphs, bar height represents the mean of (n=7–8) mice in each condition, error bars represent the sem, and asterisks (*) denote statistical significance at p<0.05 by 2×2 ANOVA (B–C) or 2×2 repeated measures ANOVA (D–E).