Transiently Aβ-induced memory deficit and its rescue with zinc chelators.
(A) The object recognition test was performed 1 h after injection of saline (control) (n = 16), Aβ (25 pmol) (n = 13), Aβ + CaEDTA (500 pmol) (n = 10), and CaEDTA (n = 9) in saline (1 µl). *, p<0.05, vs. saline, #, p<0.05 (Tukey's test). (B) The object recognition test was performed 1 h after injection of saline (control) (n = 16), Aβ (25 pmol) (n = 13), and Aβ + ZnAF2-DA (100 pmol) (n = 12) in saline (1 µl). **, p<0.01, vs. saline, #, p<0.05 (Tukey's test). (C) Brain slices were prepared 1 h after bilateral injection of ZnAF-2DA (100 pmol, 100 µM/1 µl). Intracellular ZnAF-2 fluorescence was measured as the basal level for 30 s and then measured under stimulation with 50 mM KCl for 170 s. Note that intracellular ZnAF-2 fluorescence was observed only in a few slices including the injected area in the dentate gyrus. ML, molecular layer; GCL, granule cell layer. Bars, 50 µm. (D) The data represent the rate (%) of fluorescence intensity in the dentate granule cell layer 170 s after stimulation to that before the stimulation, which was represented as 100% (n = 5). ***, p<0.001 (paired t-test). vs. base. (E and F) LTP was induced 4 h after injection of saline (n = 9), Aβ (25 pmol) (n = 6), and Aβ + ZnCl2 (50 pmol) (n = 6) in saline (1 µl). No significant difference, vs. saline (Dunnett's test). (G) Representative fEPSP recordings at the time −250 min (before injection; light grey line), −20 min (after injection; dark grey line) and 50 min (after tetanic stimulation; black line) are shown. Scale bar, vertical axis (5 mV), cross axis (10 ms). (H) The object recognition test was performed 4 h after injection of saline (control) (n = 7) and Aβ (25 pmol) (n = 8) in saline (1 µl). No significant difference, vs. saline (t-test).
