Fig. 7: ALA and EDA rescue cognition and restore lifespan of AD mice to normal levels.
a,b, Images (a) showing dendritic spines from CA1 pyramidal cells of C57/PAMAGPR120+/+, C57/PAMAGPR120−/−, PS1/PAMAGPR120+/+, PS1/PAMAGPR120−/−, PS1/PAMAGαi1+/+ and PS1/PAMAGαi1−/− mice at 8 months of age. The individual mice at 5 months of age were treated with vehicle or A-E for 45 consecutive days. Experiments were repeated at least three times independently with similar results. b, Quantification of dendritic spine densities (the number of spines per 10 μm). Data are presented as mean ± s.e.m., n = 15 neurons from 5 mice per group. ****P < 0.0001; NS, no significant difference, one-way ANOVA with Tukey’s multiple comparisons test. c–g, ALA and EDA restore LTP. EPSPs intracellularly recorded in CA1 pyramidal neurons of the slices from C57/PAMAGPR120+/+ and C57/PAMAGPR120−/− (c) or PS1/PAMAGPR120+/+ and PS1/PAMAGPR120−/− mice (d) or PS1/PAMAGαi1+/+ and PS1/PAMAGαi1−/− mice (f) treated with saline vehicle (c and d) or A-E (e and f). EPSPs evoked by stimulation of the Schaffer collateral fibers are normalized with respect to 10 min immediately preceding the tetanus (arrow). Representative traces are EPSPs immediately before (0) and 30 min after (1) the tetanus. Averages of the last 10 min of EPSPs were quantified (g). Data are presented as mean ± s.e.m., n = 18 recordings from 6 mice per group. ****P < 0.0001; NS, no significant difference, one-way ANOVA with Tukey’s multiple comparisons test. h–k, ALA and EDA restore lifespan of AD mice to normal levels. h–j, The MLE and survival curves of C57/PAMAGPR120+/+ and C57/PAMAGPR120−/− mice (h), PS1/PAMAGPR120+/+ and PS1/PAMAGPR120−/− mice (i and j) treated with control vehicle (h and i) or A-E (j). k, The MLE and survival curves of 5×FAD/PAMAGPR120+/+ (magenta and dark blue) and 5×FAD/PAMAGPR120−/− mice (light blue) treated with control vehicle (magenta) or A-E (dark blue and light blue). P < 0.0001, log-rank (Mantel–Cox) test. The exact P values are reported as source data.
