Fig. 2

AMPA treatment alters Aβ levels through multiple pathways. a APP/PS1 mice (n = 6) were treated with 100 μM NBQX, an AMPA receptor antagonist, for 8 h then co-treated with either 40 μM NMDA (n = 6), 5 μM AMPA (n = 7), or vehicle (n = 12). After 6 h of co-treatment with NBQX, the addition of AMPA had no effect on Aβ levels, though NMDA still reduced Aβ by 37.5 ± 3.3% (p < 0.0001, one-way ANOVA, Bonferroni post hoc test). b Animals (n = 6 per group) were treated with 5 μM tetrodotoxin (TTX) for 16 h then co-treated with TTX and either 5 μM AMPA, 100 μM NBQX, or vehicle for an additional 14 h. After 8 h of co-treatment, ISF Aβ levels remained unchanged in all groups. 14 h co-treatment with AMPA reduced Aβ levels by 34.6 ± 9.9% (p = 0.0027, two-way ANOVA, Sidak post hoc test) and co-treatment with NBQX reduced levels by 32.8 ± 9.3% (p = 0.0027, two-way ANOVA, Sidak post hoc test). c APP/PS1 mice were treated with either 5 μM AMPA (n = 7) or vehicle (n = 5) for 14 h, leading to a decrease in ISF Aβ levels of 66.3 ± 11.8% (p = 0.0001, two-way ANOVA, Sidak post hoc test). d 100 μM MK801 or vehicle was administered by reverse microdialysis for 6 h to APP/PS1 mice followed by co-administration with 5 μM AMPA or vehicle. After 8 h, mice treated with AMPA alone had significance decreases in ISF Aβ as compared to vehicle-treated mice, but mice receiving both MK801 and AMPA showed no change (p = 0.996, two-way ANOVA, Sidak post hoc test). After 14 h, however, AMPA treatment significantly decreased ISF Aβ levels to the same extent regardless of the presence of MK801 (p = 0.384, two-way ANOVA, Sidak post hoc test). Data plotted as mean ± SEM