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.
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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©2016 by De Gruyter
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: Kinin 2015 at São Paulo, Brazil
- Kinin 2015 – International Meeting on Kinin System and Peptide Receptors
- Kinins and microglial responses in bipolar disorder: a neuroinflammation hypothesis
- Kinins and peptide receptors
- The role of N-terminal and C-terminal Arg residues from BK on interaction with kinin B2 receptor
- Genetic analysis of hereditary angioedema in a Brazilian family by targeted next generation sequencing
- Cellular localisation of the kinin B1R in the pancreas of streptozotocin-treated rat and the anti-diabetic effect of the antagonist SSR240612
- New mutations in SERPING1 gene of Brazilian patients with hereditary angioedema
- Differential effect of intranasally administrated kinin B1 and B2 receptor antagonists in Alzheimer’s disease mice
- Kinin B1 receptor mediates memory impairment in the rat hippocampus
- Safety and pharmacokinetics of a kinin B1 receptor peptide agonist produced with different counter-ions
- Minireview
- Functional organization of human SAMHD1 and mechanisms of HIV-1 restriction
- Corrigendum
- Corrigendum to: Defects of corneocyte structural proteins and epidermal barrier in atopic dermatitis
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: Kinin 2015 at São Paulo, Brazil
- Kinin 2015 – International Meeting on Kinin System and Peptide Receptors
- Kinins and microglial responses in bipolar disorder: a neuroinflammation hypothesis
- Kinins and peptide receptors
- The role of N-terminal and C-terminal Arg residues from BK on interaction with kinin B2 receptor
- Genetic analysis of hereditary angioedema in a Brazilian family by targeted next generation sequencing
- Cellular localisation of the kinin B1R in the pancreas of streptozotocin-treated rat and the anti-diabetic effect of the antagonist SSR240612
- New mutations in SERPING1 gene of Brazilian patients with hereditary angioedema
- Differential effect of intranasally administrated kinin B1 and B2 receptor antagonists in Alzheimer’s disease mice
- Kinin B1 receptor mediates memory impairment in the rat hippocampus
- Safety and pharmacokinetics of a kinin B1 receptor peptide agonist produced with different counter-ions
- Minireview
- Functional organization of human SAMHD1 and mechanisms of HIV-1 restriction
- Corrigendum
- Corrigendum to: Defects of corneocyte structural proteins and epidermal barrier in atopic dermatitis