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. 2018 Sep 27;11(9):dmm035634. doi: 10.1242/dmm.035634

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© 2018. Published by The Company of Biologists Ltd

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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Fig. 2. — DYRK1A-specific inhibitors rescue NOR deficits induced in Tg(Dyrk1a), Ts65Dn and Dp1yey trisomic mice. (A) Duration of treatment. NOR test results for Tg(Dyrk1a) mice treated with L41 or vehicle for 5, 12 or 19 days. Percentage object exploration by sniffing was determined for each object after a 24 h retention delay (familiar object, open symbol; novel object, filled symbol). NOR results of three Tg(Dyrk1a) cohorts treated with L41 for 5 (left), 12 (centre) or 19 (right) days. Tg(Dyrk1a) and Ts65Dn treated animals spent more time exploring the novel object compared with control mice, showing a rescue of their recognition memory. Left: 5 days treatment induced a NOR rescue in Tg(Dyrk1a) animals [wt: n=15, P<0.001; treated wt: n=15, P<0.001; untreated Tg(Dyrk1a): n=11, P=0.8; treated Tg(Dyrk1a): n=13, P=0.02]. Centre: a more consistent rescue was obtained after 12 days of L41 treatment [not treated wt: n=12, P<0.001; treated wt: n=15, P=0.11; untreated Tg(Dyrk1a): n=8, P=0.76; treated Tg(Dyrk1a): n=11, P<0.001]. Right: rescue obtained after 19 days of L41 treatment: the exploration was significantly different for wt (n=15, P<0.001), treated wt (n=15, P<0.001) and treated Tg(Dyrk1a) (n=15b, P<0.001) mice, but not for nontreated transgenic mice (n=13, P=0.64). (B) Treatment with L43 (left) and L99 (right). L99 treatment induced a cognitive rescue in the Tg(Dyrk1a) mice, whereas L43 treatment had no effect. L99 (right): [wt: n=10, P=0.02; treated wt: n=12, P=0.003; Tg(Dyrk1a): n=12, P=0.01; treated Tg(Dyrk1a): n=9, P<0.001]. L43 (left): [wt: n=12, P=0.008; treated wt: n=7, P=0.9; Tg(Dyrk1a): n=13, P=0.91; treated Tg(Dyrk1a): n=12, P=0.71]. (C) Ts65Dn and Dp1yey models. Left: in the Ts65Dn study, a significant statistical difference was observed for untreated wt (n=10, P<0.001), treated wt (n=8, P=0.009) and treated Ts65Dn (n=11, P=0.002), but not for untreated Ts65Dn animals (n=9, P=0.08). Right: L41 also normalizes the recognition memory of Dp1Yey mice (wt: n=13, P=0.04; treated wt: n=14, P=0.02; Dp1Yey: n=7, P=0.98; treated Dp1Yey: n=11, P=0.03). Data are represented as mean±s.e.m. with individual points per animal. Statistical analysis was performed with the two-way ANOVA test, Tukey post hoc. n.s., not significant. *P<0.05, **P<0.01, ***P<0.001.