Increases of kinin B 1 and B 2 receptors binding sites after brain infusion of amyloid-beta 1–40 peptide in rats

Abstract

Although numerous inflammation pathways have been implicated in Alzheimer's disease, the involvement of the kallikrein–kinin system is still under investigation. We anatomically localized and quantified the density of kinin B 1 and B 2 receptors binding sites in the rat brain after the infusion of amyloid-β (Aβ) peptide in the right lateral brain ventricle for 5 weeks. The conditioned avoidance test showed a significant reduction of memory consolidation in rats infused with Aβ (68.6 ± 20.9%, P < 0.05) when compared to control group (90.8 ± 4.1%; infused with vehicle). Autoradiographic studies performed in brain samples of both groups using [ 125I]HPP-[des-Arg 10]-Hoe-140 (150 pM, 90 min, 25 °C) showed a significant increase in density of B 1 receptor binding sites in the ventral hippocampal commissure (1.23 ± 0.07 fmol/mg), fimbria (1.31 ± 0.05 fmol/mg), CA1 and CA3 hippocampal areas (1.05 ± 0.03 and 1.24 ± 0.02 fmol/mg, respectively), habenular nuclei (1.30 ± 0.04 fmol/mg), optical tract (1.30 ± 0.05 fmol/mg) and internal capsule (1.26 ± 0.05 fmol/mg) in Aβ group. For B 2 receptors ([ 125I]HPP-Hoe-140, 200 pM, 90 min, 25 °C), a significant increase in density of binding sites was observed in optical tract (2.04 ± 0.08 fmol/mg), basal nucleus of Meynert (1.84 ± 0.18 fmol/mg), lateral septal nucleus – dorsal and intermediary portions (1.66 ± 0.29 fmol/mg), internal capsule (1.74 ± 0.19 fmol/mg) and habenular nuclei (1.68 ± 0.11 fmol/mg). In control group, none of these nuclei showed [ 125I]HPP-Hoe-140 labeling. This significant increase in densities of kinin B 1 and B 2 receptors in animals submitted to Aβ infusion was observed mainly in brain regions related to cognitive behavior, suggesting the involvement of the kallikrein–kinin system in Alzheimer's disease in vivo.