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Differential effect of intranasally administrated kinin B1 and B2 receptor antagonists in Alzheimer’s disease mice

  • Keren Asraf , Nofar Torika , Ella Roasso and Sigal Fleisher-Berkovich EMAIL logo
Published/Copyright: November 9, 2015

Abstract

An Increasing body of evidence supports a critical role of brain inflammation in the pathogenesis of Alzheimer’s disease. A principal aspect of the brain immune response to inflammation is the activation of microglia. It has been shown that the kinin system is activated during brain inflammation and previously we demonstrated that bradykinin B1 receptor agonist reduced microglial activation in vitro. The aim of the present study was to investigate the effects of bradykinin B1 or B2 receptor antagonists on microglial release of pro-inflammatory factors in BV2 microglia. In vivo, we focused on the effects of intranasally given kinin antagonists on amyloid burden and microglia/macrophage marker expression in brains of 5X familial Alzheimer’s disease mice. The present data show that pharmacological antagonism of B1 receptor (R-715) but not B2 receptor (HOE-140) markedly increased nitric oxide and tumor necrosis factor alpha release from BV2 microglial cells. We also showed that intranasal treatment with R-715 but not HOE-140 of Alzheimer’s mice enhanced amyloid beta burden and microglia/macrophages activation. Taken together, our data reveal a possible role for the bradykinin B1 receptor in neuroinflammation and in the control of Abeta accumulation in transgenic mice, possibly through regulation of glial cell responses.


Corresponding author: Sigal Fleisher-Berkovich, Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva, Israel, e-mail:

Acknowledgments

We wish to thank Prof. Abraham Danon for careful reading of the manuscript and useful advice. This research was supported by the Israel Science Foundation (grants no. 101/11-15 and 101/11-16).

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Received: 2015-8-2
Accepted: 2015-11-4
Published Online: 2015-11-9
Published in Print: 2016-4-1

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