Figure 4.

Treatment with ψ-GSH dipeptide (2) restored cognitive impairment induced by i.c.v. Aβ^1–42. After initiation of compound treatment, i.c.v. injection of Aβ^1–42 was performed on day 4 and followed by continued treatment with compound 2 for 8 additional days. The T-maze spontaneous alternation test was conducted on days 10 and 11 to assess cognitive function. (A) Reduced alternation behavior was observed in saline treated Aβ-injected mice, which was restored to levels comparable to vehicle control mice with oral and i.p. treatment of 2. (B) Higher number of re-entries was evident in Aβ^1–42-injected mice. Treatment with 2 (oral and high dose i.p.) showed reduction in repetitive arm entries. (C,D) Measurement of oxidative stress in the brain tissues was performed by analysis of reduced GSH and GSH/GSSG ratio. Compound-treated mice did not differ significantly from the vehicle-treated mice. (E) Quantitation of protein carbonyls by DNPH assay showed significant reduction in protein oxidation in the compound treated groups. Data are shown as the mean ± SEM. Statistical significance was assessed by a one-way ANOVA with Tukey’s post-hoc test (* p < 0.05, ** p < 0.01, *** p < 0.005, **** p < 0.001).