title: Participation of kinin receptors on memory impairment after chronic infusion of human amyloid-beta 1-40 peptide in mice.
abstract: Chronic infusion of human amyloid-beta 1-40 (Abeta) in the lateral ventricle (LV) of rats is associated with memory impairment and increase of kinin receptors in cortical and hippocampal areas. Deletion of kinin B1 or B2 receptors abolished memory impairment caused by an acute single injection of Abeta in the LV. As brain tissue and kinin receptors could unlikely react to acute or chronic administration of a similar quantity of Abeta, we evaluated the participation of B1 or B2 receptors in memory impairment after chronic infusion of Abeta. Male C57Bl/6J (wt), knock-out B1 (koB1) or B2 (koB2) mice (12weeks of age) previously trained in a two-way shuttle-box and achieving conditioned avoidance responses (CAR, % of 50 trials) were infused with AB (550pmol, 0.12microL/h, 28days) or vehicle in the LV using a mini-osmotic pump. They were tested before the surgery (T0), 7 and 35days after the infusion started (T7; T35). In T0, no difference was observed between CAR of the control (Cwt=59.7+/-6.7%; CkoB1=46.7+/-4.0%; CkoB2=64.4+/-5.8%) and Abeta (Abetawt=66.0+/-3.0%; AbetakoB1=66.8+/-8.2%; AbetakoB2=58.7+/-5.9%) groups. In T7, AbetakoB2 showed a significant decrease in CAR (41.0+/-8.6%) compared to the control-koB2 (72.8+/-2.2%, P<0.05). In T35, a significant decrease (P<0.05) was observed in Abetawt (40.7+/-3.3%) and AbetakoB2 (41.2+/-10.7%) but not in the AbetakoB1 (64.0+/-14.0%) compared to their control groups. No changes were observed in the controls at T35. We suggest that in chronic infusion of BA, B1 receptors could play an important role in the neurodegenerative process. Conversely, the premature memory impairment of koB2 suggests that it may be a protective factor.
authors.affiliation: Department of Physiological Sciences, Faculdade de Ciências Médicas da Santa Casa de São Paulo, Rua Dr. Cesario Motta Junior, 61, São Paulo, SP, CEP 01221-020, Brazil.
authors.forename: Fabio Agostini
authors.initials: FA
authors.lastname: Amaral
authors.forename: Mayra Tolentino Resk
authors.initials: MT
authors.lastname: Lemos
authors.forename: Karis Ester
authors.initials: KE
authors.lastname: Dong
authors.forename: Maria Fernanda Queiroz Prado
authors.initials: MF
authors.lastname: Bittencourt
authors.forename: Ariadiny Lima
authors.initials: AL
authors.lastname: Caetano
authors.forename: João Bosco
authors.initials: JB
authors.lastname: Pesquero
authors.forename: Tania Araujo
authors.initials: TA
authors.lastname: Viel
authors.forename: Hudson Sousa
authors.initials: HS
authors.lastname: Buck
mesh_terms: D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008569:Memory Disorders / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage*; D043783:Receptor, Bradykinin B1 / Q000235:genetics / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; C078592:amyloid beta-protein (1-40)