Repeated administration of RGFP-966 improves short-term recognition and spatial memory in 3xTg-AD mice. Repeated administration of RGFP-966 improves short-term.

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Repeated administration of RGFP-966 improves short-term recognition and spatial memory in 3xTg-AD mice. Repeated administration of RGFP-966 improves short-term recognition and spatial memory in 3xTg-AD mice. (A) Repeated administration of RGFP-966 significantly increased mean Y-maze spontaneous alternation rate in the 3- and 10-mg/kg RGFP-966 treatment groups compared with control and (B) improved RI during the NOR test in the 10-mg/kg RGFP-966 condition compared with control. (C) Mice treated with vehicle did not improve in terms of latency to find goal box between training days 1 and 4, while the latency decreased significantly in 3- and 10-mg/kg RGFP-966 treatment groups between days 1 and 3 and between days 1 and 4. (D) 3xTg-AD mice treated with 10 mg/kg RGFP-966 committed fewer errors during the Barnes maze test probe day compared with vehicle-treated control and compared with mice treated with 3 mg/kg RGFP-966. (E) RGFP-966 increased latency to fall of the rotating rod between training days 1 and 9 in 3-mg/kg and 10-mg/kg RGFP-966 conditions. Mice treated with vehicle control did not differ significantly from the 10-mg/kg RGFP-966 condition in terms of latency to fall of the rod during the first day of training. The difference to fall of the rod was statistically different at the end of training day 9 between vehicle and the 10-mg/kg RGFP-966 condition. (F) RGFP-966 increased time spent on the balance beam during the balance beam test in RGFP-966–treated mice compared with controls. (G) 3xTg-AD mice treated with 10 mg/kg RGFP-966 built better quality nests compared with vehicle-treated controls. Images exemplify poor (nesting score = 0) and good (nesting score = 4) nes-building skills. ANOVA with Tukey’s multiple comparisons test was used for all comparisons. The graphs represent mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.001; ns, not significant; n = 5–6. Karolina J. Janczura et al. PNAS 2018;115:47:E11148-E11157 ©2018 by National Academy of Sciences