Participation of kinin receptors on memory impairment after chronic infusion of human amyloid-β 1-40 peptide in mice

Chronic infusion of human amyloid-β 1-40 (Aβ) 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 Aβ in the LV. As brain tissue and kinin receptors could unlikely react to acute or chronic administration of a similar quantity of Aβ, we evaluated the participation of B1 or B2 receptors in memory impairment after chronic infusion of Aβ. Male C57Bl/6 J (wt), knock-out B1 (koB1) or B2 (koB2) mice (12 weeks of age) previously trained in a two-way shuttle-box and achieving conditioned avoidance responses (CAR, % of 50 trials) were infused with AB (550 pmol, 0.12 μL/h, 28 days) or vehicle in the LV using a mini-osmotic pump. They were tested before the surgery (T0), 7 and 35 days 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 Aβ (Aβwt = 66.0 ± 3.0%; AβkoB1 = 66.8 ± 8.2%; AβkoB2 = 58.7 ± 5.9%) groups. In T7, AβkoB2 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 Aβwt (40.7 ± 3.3%) and AβkoB2 (41.2 ± 10.7%) but not in the AβkoB1 (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.