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-beta (A beta) 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 A beta (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 [I-125]HPP-[des-Arg(10)]-Hoe-140 (150 pM, 90 min, 25 degrees 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 A beta group. for B-2 receptors ([I-125]HPP-Hoe-140, 200 pM, 90 min, 25 degrees 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 (1.69 +/- 0.11 fmol/mg). in control group, none of these nuclei showed [I-125]HPP-Hoe-140 labeling. This significant increase in densities of kinin B-1 and B-2 receptors in animals submitted to A beta 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. (c) 2007 Elsevier Inc. All rights reserved.Fac Ciencias Med Santa Casa, Dept Physiol Sci, BR-01221020 São Paulo, BrazilFac Ciencias Med Santa Casa, Dept Pathol Sci, BR-01221020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, BR-04044020 São Paulo, BrazilWeb of ScienceFundo de Amparo a Pesquisa da Faculdade de Ciencias Medicas da Santa Casa de São Paulo (FAP-FCM)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP