In the hippocampus of the control APP-tg mice, there were many Iba-1+

and CD11b− microglia cells surrounding the senile plaques (Fig. 4a), while nasally vaccinated mice with rSeV-Aβ showed the uniform distribution of Iba-1+ CD11b+ microglia (Fig. 4b). GFAP positive cells were less frequent in mice nasally vaccinated with rSeV-Aβ. Synaptophysin immunoreactivity was shrunken and disrupted in control mice with rSeV-LacZ. The nasally vaccinated mice with rSeV-Aβ showed the amelioration of abnormal change in synaptic densities and distribution patterns (Fig. 4c and d). We examined the changes of body weight in Tg2576 mice treated with SeV-Aβ nasally at the age of 12 months. The body weight measured at the age of 15 months was 28.2 ± 1.4 g for rSeV-LacZ-vaccinated non-tg mice, 26.3 ± 1.1 g for rSeV-Aβ-vaccinated non-tg mice, 23.8 ± 0.9 g for rSeV-LacZ-vaccinated Tg2576 Talazoparib clinical trial mice, and 22.6 ± 0.7 g for rSeV-Aβ-vaccinated Tg2576 mice. Results with the two-way ANOVA were significantly different in genotype (F(1,38) = 17.08, p < 0.01) but not vaccination (F(1,38) = 2.24, p = 0.14)

nor interaction of genotype with vaccination (F(1,38) = 0.10, p = 0.74). During the training session, there were no significant differences in exploratory preference between the two objects and total exploratory time among the groups (data not shown), suggesting that all groups of mice have the same levels of motivation, curiosity, and interest in exploring INCB018424 manufacturer novel objects. For the retention session at age 12 months, the level of exploratory preference for the novel object in Tg2576 mice was significantly all decreased compared to that in non-tg mice (supplemental Fig. 1). At age 15 months, the rSeV-LacZ-vaccinated Tg2576 mice also showed a significant reduction in the exploratory preference for the novel

object compared with rSeV-LacZ-vaccinated non-tg mice, however rSeV-Aβ vaccination improved the impairment of recognition memory in Tg2576 mice significantly (supplemental Fig. 1). There was no significant difference in the number of arm entries among the groups (data not shown), suggesting that all mice have the same levels of motivation, curiosity, and motor function. At age 12 months, Tg2576 mice showed significantly reduced spontaneous alternation behavior in a Y-maze test compared with non-tg mice (Fig. 5a). At age 15 months, the rSeV-LacZ-vaccinated Tg2576 mice also showed a significant reduction in spontaneous alternation behavior compared with rSeV-LacZ-vaccinated non-tg mice, however rSeV-Aβ vaccination improved alternation behavior in Tg2576 mice significantly (Fig. 5b). In the preconditioning phase, the mice hardly showed any freezing response. There were no differences in basal levels of freezing response between the groups (data not shown).