Fig. 2

Effects of 5-HIAA on brain amyloid peptide accumulation and memory performance. a, b: Inhibitory action of 5-HIAA against phosphoramidon-induced brain Aβ accumulation in 3-month-old Swiss albino mice (n = 7 for each group). a Phosphoramidon induces an increase in Aβ 1–42 peptide which is counteracted by 5-HIAA treatment. The effect of 5-HIAA can be seen also in control mice non-treated with Phosphoramidon (see also Table 1). Statistical analysis by an ANOVA completed with a Bonferroni’s Multiple Comparison Test. * p < 0.05, ** p < 0.005, *** p < 0.0001. b: Same results than in A with the Aβ 1–40 peptide. c 5-HIAA- or 5-HTP-induced decrease of brain Aβ peptide level in 14-month-old Tg 2576/APPSWE mice (Tg). The mice (n = 7 for each group) were treated daily during 5 consecutive days with 5-HTP (48 mg/kg, I.P.) or 5-HIAA (24 μL of a 30 mM, intra-nasal). 5-HIAA treatment reduces brain 1–40 and 1–42 Aβ concentrations in wild type (WT) and APPSWE mice. 5-HTP treatment is also active in APPSWE mice (see also Table 2). The statistical analysis was done by an ANOVA completed with a Bonferroni’s Multiple Comparison Test of NT (non-treated) WT (wild-type) or Tg (Tg 2576/APPSWE) mice. d Photomicrographs showing the co-localization of NEP and 1–40 Aβ peptide in the cortex of Tg 2576/APPSWE mice brain. Scale bars: 50 μm. This image is an illustration of the distribution of NEP and amyloid deposits co-localization. e Effects of 5 consecutive days intra-nasal 5-HIAA (24 μl of a 30 mM solution) or I.P. 5-HTP (48 mg/kg) treatments on the spatial novelty performances of 14-month-old wild-type (WT) and Tg 2576/APPSWE (Tg) mice (n = 7 for each group). Results are shown as the mean additional time (SEM) spent in exploring the displaced object versus the non-displaced objects during the retention trial. This value was compared to the 0 value (no detection of the spatial change) with a Student t-test (** p < 0.01) to determine whether spatial novelty detection occurred. Treated WT mice exhibited an improved performance compared to control animals; 5-HIAA-treated mice showed the best performance. Non-treated (NT) Tg 2576/APPSWE mice performed very poorly compared to treated transgenic animals. The various groups were compared with an ANOVA (P < 0.0001) completed with a Newman-Keuls Multiple Comparison Test to evaluate the effects of treatments. Retention performances of the non-treated (NT) APPSWE groups were lower than those of treated APPSWE, treated WT and non-treated WT groups, respectively