Prevention of memory deficits in APPswe/PS1dE9 transgenic mice (Tg mice) by MgT treatment. (A) Escape latencies in seconds(s) during training (5 trials/day) in water maze task at 7 months of age, i.e., after 1 month of treatment. Three groups of mice were used; WT (nn = 9), Tg (nn=13) and Tg + MgT (nn = 9; ANOVA effect of treatment, p < 0.05). (B) Probe test conducted 24 h after the training. Top, representative path tracings. Bottom, percentage of time spent in each quadrant (ANOVA differences among quadrants; WT: p < 0.05; Tg + MgT: p<0.0001). (C) Same as (A) and on the same mice, but tested at 15 months of age. WT (nn = 9); Tg (n = 7); Tg + MgT (n = 6). ANOVA effect of treatment p< 0.05. (D) Probe test 24 h later (ANOVA differences among quadrants: WT: p < 0.0001; Tg + MgT: p < 0.0001). (E) Short-term (10 m in retention interval, left) and long-term (24 h, right) novel-object recognition memory tests performed on the same group of mice at 22 months of age. WT (nn = 7), Tg (nn = 6), and Tg + MgT (nn = 6). Recognition index calculated as percentage of time spent exploring each object (Obj1-3). Black bars indicate novel object (Nov). ANOVA differences in recognition index of different objects in WT (STM: p < 0.0001; LTM: p < 0.0001) and Tg + MgT (STM: p < 0.0001; LTM: p < 0.001). Dashed lines represent chance levels of performance (25%). (F) Total magnesium (ionized and non-ionized) contents in different organs/tissues (Mgtissue) normalized to tissue weight (mg/g) in the same groups of mice. WT (nn = 7), Tg (nn = 6) and Tg + MgT (n = 6). ANOVA difference among groups (brain: p < 0.0001; kidney: p < 0.01). (G) Magnesium ion concentration in the plasma ([Mg2+]plasma, mM) of WT (n = 14), Tg (n = 9) and Tg + MgT mice (n = 8) as measured by the calmagite method. ANOVA difference among groups (p < 0.01). (H) The intracellular free Mg2+ concentration in the red blood cell ([Mg2+]RBC) of WT (n = 12), Tg (n = 11) and Tg + MgT mice (n = 11) as measured by the flow cytometry method (fluorescent optical density, OD). ANOVA difference among groups (p < 0.05). ANOVA was followed by Bonfferoni's post hoc test. (I) Brain total magnesium content (Mgbrain, mg/g), in Tg mice (23 months old), significantly correlated with the recognition index in the short-term recognition memory test (Pearson's test). Data from Tg + MgT mice (23 months old treated for 17 months) are displayed, but were not included in the correlation analysis. Error bars show SEM. * p < 0.05, *** p < 0.001.