Fig. 2: Ovariectomy persuaded recall deficits and induced impairment of local activity dependent protein translation after contextual fear conditioning in APP/PS1 female mice at 4 months of age.

Sham or ovariectomized WT and APP/PS1 female mice were subjected contextual fear conditioning at 4- and 8-months age and assessed their recall memory as described in methods section. A Impairment in freezing response was observed in OVX APP/PS1 female mice following contextual fear conditioning at 4 months of age with comparison to all other groups as examined. (WT-Sham versus APP/PS1-Sham, p = 0.7251; WT-Sham versus WT-OVX, p = 0.2798; APP/PS1-Sham versus APP/PS1-OVX, p = 0.0005; WT-Sham versus APP/PS1-OVX, p = 0.0086; WT-OVX versus APP/PS1-OVX, p < 0.0001). Partial Eta squared = 0.353. n = 10 mice per group. B Sham or OVX APP/PS1 female mice exhibit significantly decreased freezing response than the sham or OVX WT female mice at 8 months of age. n = 5–7 mice per group. Statistical comparison is performed using two-way ANOVA. (WT-Sham versus APP/PS1-Sham, p < 0.0001; WT-Sham versus WT-OVX, p = 0.3835; APP/PS1-Sham versus APP/PS1-OVX, p = 0.4522; WT-Sham versus APP/PS1-OVX, p = 0.0005; WT-OVX versus APP/PS1-OVX, p = 0.0146). Partial Eta squared=0.197. Data are presented as mean ± s.e.m. Statistical significance indicated as *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. n = 5–7 mice per group. Protein translation in synaptoneurosomes from sham or OVX WT and APP/PS1 female mice after KCl stimulation was measured as L-[³⁵S]-methionine incorporation. C L-[³⁵S]-methionine incorporation by KCl stimulation was significantly increased in synaptoneurosomes from sham WT or APP/PS1 female mice (4 months) than unstimulated synaptoneurosomes. KCl stimulated protein translation was significantly impaired in synaptoneurosomes from OVX APP/PS1 female mice (4 months) than unstimulated OVX APP/PS1 female mice (4 months). Statistical comparisons from each group (unstimulated versus stimulated) were calculated using paired, one-sided, student t-test. All values normalized to unstimulated WT-sham group. (WT-Sham-US versus WT-Sham-St, t = 5.442; df = 4; p = 0.003; Hedges’ g (95% CI) 2.79 (1.01, 4.51); WT-OVX-US versus WT-OVX-St, t = 2.649; df = 4; p = 0.029; Hedges’ g (95% CI) 0.79 (−0.41, 1.95); APP/PS1-Sham-US versus APP/PS1-Sham-St, t = 6.62; df = 4; p = 0.001; Hedges’ g (95% CI) 1.69 (0.27, 3.04); APP/PS1-OVX-US versus APP/PS1-OVX-St, t = 0.06526; df = 4; p = 0.476; Hedges’ g (95% CI) −0.01 (−1.13, 1.10)). Data are presented as mean ± s.e.m. Statistical significance indicated as *p < 0.05. n = 5 mice per group.