Kinin B1 receptor mediates memory impairment in the rat hippocampus

Abstract

The bradykinin (BK) receptors B1R and B2R are involved in inflammatory responses and their activation can enhance tissue damage. The B2R is constitutively expressed and mediates the physiologic effects of BK, whereas B1R expression is induced after tissue damage. Recently, they have been involved with Alzheimer's disease, ischemic stroke and traumatic brain injury (TBI). In this study, we investigated the role of bradykinin in short and long-term memory consolidation (STM and LTM). It was observed that bilateral injection of BK (300 pmol/μl) disrupted the STM consolidation but not LTM, both evaluated by inhibitory avoidance test. The STM disruption due to BK injection was blocked by the previous injection of the B1R antagonist des-Arg10-HOE140 but not by the B2R antagonist HOE140. Additionally, the injection of the B1 agonist desArg9-BK disrupted STM and LTM consolidation at doses close to physiological concentration of the peptide (2.3 and 37.5 pmol, respectively) which could be reached during tissue injury. The presence of B1R located on glial cells around the implanted guide cannula used for peptide injection was confirmed by immunofluorescence. These data imply in a possible participation of B1R in the STM impairment observed in TBI, neuroinflammation and neurodegeneration.

Kinin B2 Receptor Activation Prevents the Evolution of Alzheimer’s Disease Pathological Characteristics in a Transgenic Mouse Model

“…The hippocampal slices were treated with BK, B1R antagonist, B2R antagonist, and BK plus B1R antagonist. In this last combination, the B1R antagonist was added considering the possible activity of tissue carboxypeptidase M-like enzymes converting BK into the BKB1R agonist desArg9-BK [ 14 ]. Kinin B2R antagonist was used to block the effect of endogenous BK.…”

“…Every three days, the culture medium containing the treatments was replaced. The B1R antagonist [desArg10]-Hoe140 was added considering the possible activity of tissue carboxypeptidase M-like enzymes converting BK into the BKB1R agonist desArg 9 -BK [ 14 ].…”

Neuroprotective Effects of Kinin B2 Receptor in Organotypic Hippocampal Cultures of Middle-Aged Mice

“…After 1 week of stabilization, OHCs from 6-month-old (6-OHC) and 12-month-old (12-OHC) animals were treated with 300 pM of BK or 300 pM of BK + 200 pM of B1 antagonist (BK+AntB1) [AntB1: (desArg10)-Hoe140] [3-4hydroxyphenyl-propionyl-des-Arg9-D_Arg (Hyp3, Thi5, D-TiC7, Oic8)_BK], to block the possible effects of desArg9BK (Wirth et al, 1991; Dong-Creste et al, 2016), added to 1 mL of maintenance culture medium, all purchased from Sigma ® , and were treated for 30 days. Every 3 days the culture medium containing the treatments was replaced.…”

“…The BK dose used, 300 pmol, was determined based on data from the literature (Noda et al, 2007) and considering unpredictable actions of the peptidases activity in heated serum and in the brain tissue. The addition of [desArg10]-Hoe140 was performed considering the possible activity of tissue carboxypeptidase M-like enzymes converting BK into the B1R agonist desArg9-BK (Dong-Creste et al, 2016; Haddad and Couture, 2017).…”

“…It was observed that in 12-month-old KOB1 mice memory was preserved when compared to C57Bl/6 animals, however, age-matched KOB2 animals did not show the same performance in behavioral tests (Lemos et al, 2010). It was also suggested that kinin B1 receptor (BKB1R) participated in the impairment of short-term memory in traumatic brain injury in rats (Dong-Creste et al, 2016), while kinin B2 receptor (BKB2R) played a possible neuroprotective role in AD. Chronic infusion of Aβ peptide in KOB2 led to accelerated cognitive deficit and increased AB deposition when compared to KOB1 mice.…”