Increases of kinin B1 and B2 receptors binding sites after brain infusion of amyloid-beta 1-40 peptide in rats.
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 (Abeta) 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 Abeta (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 [(125)I]HPP-[des-Arg(10)]-Hoe-140 (150pM, 90min, 25 degrees C) showed a significant increase in density of B(1) receptor binding sites in the ventral hippocampal commissure (1.23+/-0.07fmol/mg), fimbria (1.31+/-0.05fmol/mg), CA1 and CA3 hippocampal areas (1.05+/-0.03 and 1.24+/-0.02fmol/mg, respectively), habenular nuclei (1.30+/-0.04fmol/mg), optical tract (1.30+/-0.05fmol/mg) and internal capsule (1.26+/-0.05fmol/mg) in Abeta group. For B(2) receptors ([(125)I]HPP-Hoe-140, 200pM, 90min, 25 degrees C), a significant increase in density of binding sites was observed in optical tract (2.04+/-0.08fmol/mg), basal nucleus of Meynert (1.84+/-0.18fmol/mg), lateral septal nucleus - dorsal and intermediary portions (1.66+/-0.29fmol/mg), internal capsule (1.74+/-0.19fmol/mg) and habenular nuclei (1.68+/-0.11fmol/mg). In control group, none of these nuclei showed [(125)I]HPP-Hoe-140 labeling. This significant increase in densities of kinin B(1) and B(2) receptors in animals submitted to Abeta 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.
Viel
Tania Araujo
TA
Department of Physiological Sciences, Faculdade de Ciências Médicas da Santa Casa de São Paulo, Sao Paulo, Brazil. taniaviel@usp.br
Lima Caetano
Ariadiny
A
Nasello
Antonia Gladys
AG
Lancelotti
Carmen Lucia
CL
Nunes
Viviane Abreu
VA
Araujo
Mariana Silva
MS
Buck
Hudson Sousa
HS
D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D007263:Infusions, Parenteral; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1 / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D014018:Tissue Distribution
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; C078592:amyloid beta-protein (1-40)