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S1/2<sup>-/-</sup> mice display novelty induced hyperactivity, decreased anxiety and exploratory behavior and working memory disturbances.

By Paul C. Baier (650225), Magdalena M. Brzózka (650226), Ali Shahmoradi (650227), Lisa Reinecke (84414), Christina Kroos (650228), Sven P. Wichert (271336), Henrik Oster (106880), Michael C. Wehr (267844), Reshma Taneja (271338), Johannes Hirrlinger (245824) and Moritz J. Rossner (267848)


<p>A–C) Open field test performed in a novel, unfamiliar test arena. WT: n = 24, S1/2<sup>-/-</sup>: n = 26. A) Novelty-induced hyperactivity in S1/2<sup>-/-</sup> mice as assessed by moving distance in the open field (p<sub>MW</sub> = 0.0006). B) Analysis in 1 min bins yielded a significant E<sub>genotype</sub> (F<sub>(1,48)</sub> = 16.46; p = 0.0002). Moreover, Bonferroni posttest revealed the strongest difference between the genotypes in interval 3, 5 and 10 (p<sub>Bonf</sub><0.01, p<sub>Bonf</sub><0.05 and p<sub>Bonf</sub><0.05, respectively). C) Mutants spent more time in the center (p<sub>MW</sub> = 0.0004) of the test arena indicating reduced anxiety when compared to controls. D-E) Hole board test performed with a subsequent modification of the open field setup by floor insert with holes. WT: n = 24, S1/2<sup>-/-</sup>: n = 26. D) S1/2<sup>-/-</sup> mice displayed no alterations in the overall activity measured as total distance travelled. E) S1/2<sup>-/-</sup> mice performed less nose pokes into holes (p<sub>MW</sub> = 0.0014) indicating decreased curiosity-related behavior compared to WT. F-G) Y-maze test. WT: n = 23, S1/2<sup>-/-</sup>: n = 20. F) S1/2<sup>-/-</sup> mice showed increased activity in Y-maze test (E<sub>genotype</sub> F<sub>(1,41)</sub> = 10.98; p = 0.0019) most evident in interval 0-5 min (p<sub>Bonf</sub><0.01). G) Mutant mice performed less alterations in Y-maze than control animals (E<sub>genotype</sub> F<sub>(1,41)</sub> = 4.86; p = 0.0331) and p<sub>Bonf</sub><0.05 for interval 5–10 min. H-J) S1/2<sup>-/-</sup> mice display impairment of working memory in the radial arm water maze (RAWM). WT: n = 29, S1/2<sup>-/-</sup>: n = 28. H) In the visible platform task, performance was similar in both genotypes (E<sub>genotype</sub> F<sub>(1,55)</sub> = 0.65; p = 0.4236). I-J) S1/2<sup>-/-</sup> mice showed increased number of working errors searching for a hidden platform on the first (I) (E<sub>genotype</sub> F<sub>(1,55)</sub> = 3.93; p = 0.0524; I<sub>genotype×time</sub> F<sub>(3,165)</sub> = 2.68; p = 0.0486) and the second (J) day of experiment (E<sub>genotype</sub> F<sub>(1,55)</sub> = 9.05; p = 0.0044) and I<sub>genotype×time</sub> F<sub>(5,275)</sub> = 2.34; p = 0.0422). Bonferroni posttest revealed significant difference during the 3<sup>rd</sup> trial of the second day (p<sub>Bonf</sub><0.001). WT, black bars/circles. S1/2<sup>-/-</sup>, white bars/circles. Data were analyzed with 2-way ANOVA with Bonferroni posttest (p<sub>Bonf</sub>) and Mann-Whitney test (p<sub>MW</sub>) for pairwise comparisons. ***: p<0.001; **: p<0.01; *: p<0.05. E, effect; I, interaction of factors.</p

Topics: Biological Sciences, SHARP 1, Mixed State Endophenotypes, clock genes, EEG recordings, per, Circadian Modulators SHARP 1, SHARP 2 Display Altered Sleep, gene expression signatures
Year: 2014
DOI identifier: 10.1371/journal.pone.0110310.g004
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Provided by: FigShare
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