Fig. 1: Impairment in recall memory after contextual fear conditioning depends on sex and age of APP/PS1 mice. | Translational Psychiatry

Fig. 1: Impairment in recall memory after contextual fear conditioning depends on sex and age of APP/PS1 mice.

From: Sex difference in evolution of cognitive decline: studies on mouse model and the Dominantly Inherited Alzheimer Network cohort

Fig. 1

A Histograms are showing the freezing response of female mice at different ages. Freezing response was assessed by contextual fear conditioning as percentage of immobility after 24 h of training and no significant difference was observed in 2 M (t = 0.2923; df = 14; p = 0.7744; Hedges’ g (95% CI) 0.14 (−0.79, 1.06)), 4 M (p = 0.4255; Hedges’ g (95% CI) 0.39 (−0.54, 1.32)) and 6 M (p = 0.1419; Hedges’ g (95% CI) −0.37 (−1.37, 0.63)) old APP/PS1 female mice compared with WT female mice. Impairment in freezing response was observed in 8 M (t = 3.794; df = 14; p = 0.0020; Hedges’ g (95% CI) −1.79 (−2.9, −0.63)), 10 M (t = 4.538; df = 14; p = 0.0005; Hedges’ g (95% CI) −2.14 (−3.33, −0.90)), and 12 M (t = 4.65; df = 14; p = 0.0004; Hedges’ g (95% CI) -2.19 (−3.40, −0.94)) old APP/PS1 female mice compared with age matched WT female mice. Statistical analysis: Two-sided t-test or Mann-Whitney U-test was applied to compare WT versus APP/PS1 mouse groups. In all panels, reported values are mean ± s.e.m. *P < 0.05. A, B n = 5–8 mice per group. B Histograms are showing the freezing response of male mice at different ages, and APP/PS1 male mice exhibit significantly decreased freezing response than the WT male from 2 months onwards. WT versus APP/PS1 male mice, 2 M (t = 4.594; df = 14; p = 0.0004; Hedges’ g (95% CI) −2.17 (−3.37, −0.92)), 4 M (t = 3.168; df = 10; p = 0.01; Hedges’ g (95% CI) −1.68 (−2.93, −0.38)), 6 M (p = 0.0317; Hedges’ g (95% CI) −1.90 (−3.32, −0.42)), 8 M (p = 0.0002; Hedges’ g (95% CI) −3.33 (−4.85, −1.78)), and 12 M (t = 4.824; df = 14; p = 0.0003; Hedges’ g (95% CI) −2.28 (−3.50, −1.01)). Statistical analysis: Two-sided t-test or Mann–Whitney U-test was used to compare WT versus APP/PS1 mouse groups. In all panels, reported values are mean ± s.e.m. *P < 0.05. A, B n = 5–8 mice per group. Local activity dependent protein translation at the synapse is significantly affected in APP/PS1 female mice at 8 months but not at 4 months of age. Synaptoneurosomes from WT and APP/PS1 female mice were stimulated with or without KCl in the presence of 50 μCi L-[35S]-methionine at 37 °C for 15 min and newly synthesized proteins (protein translation) were measured by L-[S35]-methionine incorporation assay. C KCl stimulated local protein translation in synaptoneurosomes was not affected between WT and APP/PS1 female mice at 4 months of age (WT-US versus WT-St, t = 6.894; df = 3; p = 0.003; Hedges’ g (95% CI) 4.61 (1.78, 7.40); APP/PS1-US versus APP/PS1-St, t = 3.042; df = 3; p = 0.028; Hedges’ g (95% CI) 2.59 (0.68, 4.42)). Statistical comparisons from each group (unstimulated versus stimulated) were calculated using paired, one-sided, student t-test. n = 4 mice per group. D Stimulation of local protein translation in synaptoneurosomes in the presence of KCl was impaired in APP/PS1 female mice with comparison to WT female mice at 8 months of age (WT-US versus WT-St (t = 2.960; df = 8; p = 0.009; Hedges’ g (95% CI) 0.72 (−0.19, 1.63)); APP/PS1-US versus APP/PS1-St (t = 0.341; df = 7; p = 0.372; Hedges’ g (95% CI) −0.19 (−1.11, 0.74))). Statistical comparisons from each group (unstimulated versus stimulated) were calculated using paired, one-sided, student t-test. All values normalized to unstimulated WT group. Data is represented as mean ± s.e.m. (n = 8–9 mice per group) and *denotes values significantly different from corresponding controls (p < 0.05).

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