Quantification analyses showed that area but not number of Aβ plaques were decreased ( P = 0.0072, and P = 0.0115, respectively) compared to non-treated APP/PS1 mice, suggesting that donepezil exhibits weak inhibitory effect against Aβ aggregation. Two-way repeated measures ANOVA test showed a significant genotype effect ( F(1, 14) = 72.86, P. We subjected the mice to weekly Y-maze tests during the EPPS treatment and recorded the sequences of arm entries to analyse the percent alternations reflecting spatial working memory of mice. To determine the minimum duration and dosage of EPPS administration for its therapeutic effect, the lower dosages of EPPS (0, 0.1, 1, and 10 mg/kg/day, n = 5, 7, 9, and 9, respectively) were administered orally to APP/PS1 mice daily for 10 weeks. In the previous study, we observed clearance of Aβ aggregates and recovery of cognitive impairments in the same mouse model by long-term administration of EPPS in 10, 30 and 100 mg/kg/day. The APP/PS1 model is known to show elevated levels of human Aβ by 6–7 months and impaired memory after 8 months of age. EPPS restores cognitive function of APP/PS1 mice within 4 weeks Aged APP/PS1 model mice (male, 50 weeks of age) and their age-matching wild-type (WT, n = 11) controls were used in this study. We also measured the levels of Aβ plaques and oligomers by histochemistry and sandwich enzyme-linked immunosorbent assay (ELISA).
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