Fig. 1

GEE preserves cognitive capacity and synaptic plasticity in offspring of 3XTg AD mice. (a) The experimental procedure: female 3 × Tg AD mice were mated with males, and then the pregnant females were housed in an enriched (GEE) or standard environment (Ctrl). After about 19 days of pregnancy, the EE was removed. The GEE or Ctrl F1 AD offering and age-matched wildtype (WT) mice were raised in a standard environment from weaning until 7 m of age, and then spatial learning and memory were tested in the Morris water maze (MWM). (b-e) GEE preserves spatial learning (b) and memory (c and d) without changing motor function (e) in AD offspring (WT, n = 8, Ctrl, n = 12, GEE, n = 12, from at least 4 independent litters, two–way ANOVA, Bonferroni’s post hoc test). (f,g) GEE increases protein levels of GluN2A, GluA1, GluA2 and synaptotagmin without changing GluN2B, PSD93, PSD95, synaptophysin and synapsin-1 in the hippocampus of 7 m-old offspring (from at least 3 independent litters, unpaired t-test with Welch’s correction). (h) Representative images of dendritic spines in CA1 neurons measured by Golgi staining (scale bars, 10 μm). (i) GEE increases spine density in the CA1 subset (at least 14 neurons from 6~7 mice were analyzed in each group, unpaired t-test with Welch’s correction). (j-l) GEE enhances basal synaptic transmission, as shown by an increased input–output response with potentiation of LTP indicated by an increased slope of the evoked fEPSP; the increase was still significant at 60 min after high frequency stimulation (HFS) (n = 10–12 hippocampal slices from 6~7 mice in each group, unpaired t-test with Welch’s correction). Data are presented as the mean ± s.e.m. *P < 0.05, **P < 0.01 vs. Ctrl