Figure 6

Ubc9 transduction rescues hippocampal-dependent spatial learning and memory in AD mouse models.

(a) Contextual fear conditioning behavioral task with acute Aβ infusion model. Cannulated mice were each infused with 2 treatments: 1) 15 minutes prior to foot shock training and 2) immediately afterwards. Treatment groups include (infusion 1 + infusion 2): vehicle (PBS) + vehicle (n = 22), vehicle + TAT-Ubc9 (n = 13), Aβ₄₂ oligomers + vehicle (n = 14); Aβ₄₂ oligomers + TAT-Ubc9 (n = 13). ANOVA of % freezing behavior 24 hours after foot shock training p = 0.002; *p < 0.05 versus all other groups. (b) Radial arm water maze behavioral task with acute Aβ infusion model. Cannulated mice were infused for training sessions 1 and 6 with 2 treatments: 1) 15 minutes prior and 2) immediately after the session. Treatment groups include (infusion 1 + infusion 2): vehicle (PBS) + vehicle (n = 8), vehicle + TAT-Ubc9 (n = 8), Aβ₄₂ oligomers + vehicle (n = 7); Aβ₄₂ oligomers + TAT-Ubc9 (n = 8). ANOVA of number of errors p = 0.0002; *Aβ + vehicle group p < 0.05 versus all other groups. (c) Contextual fear conditioning behavioral task with Tg2576 mice. Cannulated APP and wild-type (WT) mice were infused with 3 treatments: 1) 2 hours prior to foot shock training, 2) 20 minutes prior and 3) immediately afterwards. WT vehicle (PBS) n = 11, WT TAT-Ubc9 n = 13, APP vehicle n = 13; APP TAT-Ubc9 n = 13. ANOVA of % freezing behavior 24 hours after foot shock training p < 0.0001; *p < 0.05 versus all other groups. (d) Radial arm water maze behavioral task with Tg2576 mice. Cannulated APP and WT mice were infused for training sessions 1 and 6 with 3 treatments: 1) 2 hours prior to the session, 2) 20 minutes prior and 3) immediately after the session. WT vehicle (PBS) n = 11, WT TAT-Ubc9 n = 14, APP vehicle n = 13; APP TAT-Ubc9 n = 14. ANOVA of number of errors p < 0.0001; *APP vehicle group p < 0.05 versus all other groups. Data presented as means ± SEM; n.s. = not significant. See also Supplementary Figure S6.