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. Author manuscript; available in PMC: 2021 Sep 1.
Published in final edited form as: Sci Transl Med. 2020 Aug 26;12(558):eaaz5677. doi: 10.1126/scitranslmed.aaz5677

Fig. 8. Kdm6a overexpression in hippocampus attenuates male vulnerability to cognitive impairments in XY-hAPP mice.

Fig. 8.

(A) Experimental strategy: XY mice were gonadectomized and injected with lentivirus expressing control or overexpressing Kdm6a (Kdm6a OE) into the dentate gyrus of the hippocampus; animals were then tested on behavioral tasks. (B) Shown is Kdm6a mRNA expression measured in dentate gyrus of mice injected with lentivirus expressing control or overexpressing Kdm6a (Kdm6a OE) (n = 3 mice per experimental group), relative to XY control; t test, *P < 0.05. (C to F) Spatial learning task results for the four experimental groups of XY mice tested in the Morris water maze (age 5 to 5.5 months; n = 7 to 15 per group). XY-hAPP-Kdm6a-OE mice exhibited (C) decreased latency to find the target escape platform (mixed-model ANOVA: XY-hAPP-CTL versus XY-hAPP-Kdm6a-OE, P < 0.001) and (D) a better learning index of latency during hidden platform training, measured by the difference in performance of each mouse at day 4 from average group performance on day 1 (D1 to D4). (E) XY-hAPP-Kdm6a-OE mice did not travel a statistically decreased distance to find the target platform but (F) showed better learning in the distance traveled during hidden platform training. (G and H) Probe trial results 24 hours after completion of hidden platform learning, indicating spatial memory of the escape platform location, showed that XY-hAPP-Kdm6a-OE mice had attenuated spatial deficits including decreased (G) latency to target platform and (H) increased number of entries into the target zone, compared to XY-hAPP-CTL mice. *P < 0.05; **P < 0.01; ***P < 0.001 [Bonferroni-Holm for (G) and (H)]. Data are presented as means ± SEM.