B2 receptor blockage prevents Aβ-induced cognitive impairment by neuroinflammation inhibition

Bicca, M. A., Costa, R., Loch-Neckel, G., Figueiredo, C. P., Medeiros, R. and Calixto, J. B. (2015) B2 receptor blockage prevents Aβ-induced cognitive impairment by neuroinflammation inhibition. Behavioural Brain Research, 278 482-491. doi:10.1016/j.bbr.2014.10.040

Author Bicca, M. A.
Costa, R.
Loch-Neckel, G.
Figueiredo, C. P.
Medeiros, R.
Calixto, J. B.
Title B2 receptor blockage prevents Aβ-induced cognitive impairment by neuroinflammation inhibition
Journal name Behavioural Brain Research   Check publisher's open access policy
ISSN 0166-4328
Publication date 2015-02-01
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.bbr.2014.10.040
Open Access Status Not yet assessed
Volume 278
Start page 482
End page 491
Total pages 10
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Language eng
Formatted abstract
Background and purpose: Aβ-induced neuronal toxicity and memory loss is thought to be dependent on neuroinflammation, an important event in Alzheimer's disease (AD). Previously, we demonstrated that the blockage of the kinin B2 receptor (B2R) protects against the memory deficits induced by amyloid β (Aβ) peptide in mice. In this study, we aimed to investigate the role of B2R on Aβ-induced neuroinflammation in mice and the beneficial effects of B2R blockage in synapses alterations.

Experimental approach:
The selective kinin B2R antagonist HOE 140 (50pmol/site) was given by intracerebroventricular (i.c.v.) route to male Swiss mice 2h prior the i.c.v. injection of Aβ1-40 (400pmol/site) peptide. Animals were sacrificed, at specific time points after Aβ1-40 injection (6h, 1 day or 8 days), and the brain was collected in order to perform immunohistochemical analysis. Different groups of animals were submitted to behavioral cognition tests on day 14 after Aβ1-40 administration.

Key results: In this study, we report that the pre-treatment with the selective kinin B2R antagonist HOE 140 significantly inhibited Aβ-induced neuroinflammation in mice. B2R antagonism reduced microglial activation and the levels of pro-inflammatory proteins, including COX-2, iNOS and nNOS. Notably, these phenomena were accompanied by an inhibition of MAPKs (JNK and p38) and transcription factors (c-Jun and p65/NF-κB) activation. Finally, the anti-inflammatory effects of B2R antagonism provided significant protection against Aβ1-40-induced synaptic loss and cognitive impairment in mice.

Conclusions and implications: Collectively, these results suggest that B2R activation may play a critical role in Aβ-induced neuroinflammation, one of the most important contributors to AD progression, and its blockage can provide synapses protection.
Keyword B2 receptor
Alzheimer’s disease
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 31 May 2017, 16:34:54 EST by Kirstie Asmussen on behalf of Queensland Brain Institute