Fig. 3: Treatment of 5xFAD mice with MS1262 rescues behavioral deficits.
A Experimental timeline for drug administration and novel place recognition test. B Depiction of the paradigm used to test memory and affective related behavior. C Locomotion in an open field was unaffected under wild-type, 5xFAD, vehicle, and chronic MS1262 treatment. D Preference for the novel-located object during retrieval was significantly reduced in 5xFAD mice compared with wild-type controls and was completely rescued by chronic MS1262 treatment, as measured by discrimination ratio (see “Methods” for calculations). E Time spent in the center of an open field was unaffected under wild-type, 5xFAD, vehicle, and chronic MS1262. F MS1262 administration rescued anxiety-like behavior in 5xFAD mice back to wild-type levels demonstrated by increased time spent in the open arms of a zero maze. G Depressive-like behavioral deficits in 5xFAD mice were rescued to wildtype levels after chronic MS1262 treatment as measured by immobile time during the forced swimming paradigm. H Locomotion in an open field was unaffected under wildtype, APPNLGF, vehicle, and chronic MS1262 treatment. I Preference for the novel-located object during retrieval was significantly reduced in APPNLGF mice compared to wildtype controls and was rescued by chronic MS1262 treatment as measured by discrimination ratio. J Time spent in the center of an open field was unaffected under wildtype, APPNLGF, while chronic MS1262 treatment led to an increase in time spent in the center. K MS1262 administration rescued anxiety-like behavior in APPNLGF mice back to wildtype levels demonstrated by increased time spent in the open arms of a zero maze. L Depressive-like behavioral deficits in APPNLGF mice were rescued to wildtype levels after chronic MS1262 treatment as measured by immobile time during the forced swimming paradigm. Data are visualized as mean +/- SEM with each individual displayed as a point. Wildtype (C57BL/6 J) (n = 7), 5xFAD (n = 10), 5xFAD vehicle (n = 14), 5xFAD MS1262 (n = 12) and Wildtype (C57BL/6J-Aw-J/J) (n = 7), APPNLGF vehicle (n = 10), APPNLGF MS1262 (n = 10), mice were utilized for behavioral studies. Significance was assessed by ANOVA and two-sided Tukey’s posthoc test between each condition. ns = not significant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. (See also Figures. S4 & S5 & Data S3).
