Figure 6
3,6′-Dithiothalidomide (56 mg/kg i.p.) prevented Aβ 1–42 peptide-induced memory defects, neuronal cell degeneration and associated elevated CD11b staining of microglial cells. After 7 days of drug administration, aggregated Aβ1–42 peptide was administered directly into the CNS (and reverse peptide Aβ42–1 was utilized as a control) (for aggregation/aging process, see [32, 41]). Mouse memory function was assessed by the Morris Water Maze; escape latencies measured over a 4-day trial period (A) and the final assessment undertaken 24 h after the last training session are shown (B n = 8). (C) After the completion of behavioral assessments mice were euthanized, and the levels of neuronal degeneration were indicated by determining the level of Fluoro-Jade B labeling in the dentate gyrus; Aβ1–42 peptide induced a significant degree of dye incorporation that was attenuated by 3,6′-dithiothalidomide (n = 3–4). (D) Numbers of CD11b-positive cells in the CA3 hippocampus region were determined to be elevated only in the vehicle + Aβ1–42 group (n = 3–4). (E) Representative photomicrographs of Fluoro-Jade B-positive neurons in the dentate gyrus of control (vehicle-treated Aβ42–1-injected) mice, vehicle-treated Aβ1–42-injected mice and 3,6′-dithiothalidomide-treated Aβ1–42-injected mice. *Indicates comparisons with control (vehicle-treated Aβ42–1-injected) mice; #indicates comparisons with 3,6′-dithiothalidomide-treated Aβ1–42-injected mice (n = 3–4). Data are expressed as mean ± SEM of n observations; levels of statistical significance are indicated as follows: * or #P < 0.05, ** or ##P < 0.01, *** or ###P < 0.001.