Fig. 4

Amylovis-201 attenuated Aβ25–35-induced learning impairment in mice and Aβ25–35-induced cytotoxicity in SH-SY5Y cells through σ1 agonism: dose–response effects in the (a) spontaneous alternation in the Y-maze and (b) step-through passive avoidance. (c, d) Blockade of Amylovis-201 effect by NE-100 in each test. Mice received oligomerized Aβ25–35 peptide (9 nmol, icv) or vehicle solution and then Amylovis-201 (0.3–3 mg/kg ip) 7 days before behavioral analyses. The Y-maze session was performed on Day 7 (a, c) and passive avoidance training on Day 8 and retention on Day 9 (b, d). In (c, d), NE-100 was administered at 3 mg/kg ip simultaneously with Amylovis-201 at 3 mg/kg IP. (e) SH-SY5Y neuroblastoma cells (10,000 cells/well) were exposed to Aβ25–35 (25 μmol/L) and Amylovis-201 (0.3–3 μmol/L) and/or NE-100 (3, 10 μmol/L). Cell survival was monitored after 24 h using the MTT assay. Abbreviations: V, vehicle solution (physiological saline); A, Amylovis-201; N, NE-100. Data show mean ± SEM of the number of determination indicated within or below the columns. ANOVAs: F(5,90) = 3.336, P = 0.0082 in (a); F(4,72) = 5.109, P = 0.0011 in (c); F(11,80) = 49.51, P < 0.0001 in (e). Kruskal–Wallis ANOVAs: H = 13.5, P = 0.0019 in (b); H = 14.18, P = 0.007 in (d). ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001 vs. (V + V)-treated mice or untreated cells; #P < 0.05, ##P < 0.01, ###P < 0.001 vs. (Aβ25–35+V)-treated mice or cells; §P < 0.05, §§§P < 0.001 vs. (Aβ25–35 +Amylovis-201)-treated mice or cells; Dunnett's test in (a, c, e), Dunn's test in (b, d).