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Kinin B2 Receptor Activation Prevents the Evolution of Alzheimer’s Disease Pathological Characteristics in a Transgenic Mouse Model
Background: Alzheimer’s disease is mainly characterized by remarkable neurodegeneration in brain areas related to memory formation. This progressive neurodegeneration causes cognitive impairment, changes in behavior, functional disability, and even death. Our group has demonstrated changes in the ka...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601323/ https://www.ncbi.nlm.nih.gov/pubmed/33019732 http://dx.doi.org/10.3390/ph13100288 |
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author | Nunes, Marielza Andrade Toricelli, Mariana Schöwe, Natalia Mendes Malerba, Helena Nascimento Dong-Creste, Karis Ester Farah, Daniela Moura Azevedo Tuma De Angelis, Katia Irigoyen, Maria Claudia Gobeil, Fernand Araujo Viel, Tânia Buck, Hudson Sousa |
author_facet | Nunes, Marielza Andrade Toricelli, Mariana Schöwe, Natalia Mendes Malerba, Helena Nascimento Dong-Creste, Karis Ester Farah, Daniela Moura Azevedo Tuma De Angelis, Katia Irigoyen, Maria Claudia Gobeil, Fernand Araujo Viel, Tânia Buck, Hudson Sousa |
author_sort | Nunes, Marielza Andrade |
collection | PubMed |
description | Background: Alzheimer’s disease is mainly characterized by remarkable neurodegeneration in brain areas related to memory formation. This progressive neurodegeneration causes cognitive impairment, changes in behavior, functional disability, and even death. Our group has demonstrated changes in the kallikrein–kinin system (KKS) in Alzheimer’s disease (AD) experimental models, but there is a lack of evidence about the role of the KKS in Alzheimer’s disease. Aim: In order to answer this question, we evaluated the potential of the kinin B2 receptors (BKB2R) to modify AD characteristics, particularly memory impairment, neurodegeneration, and Aβ peptide deposition. Methods: To assess the effects of B2, we used transgenic Alzheimer’s disease mice treated with B2 receptor (B2R) agonists and antagonists, and performed behavioral and biochemical tests. In addition, we performed organotypic hippocampal culture of wild-type (WT) and transgenic (TG) animals, where the density of cytokines, neurotrophin BDNF, activated astrocyte marker S100B, and cell death were analyzed after treatments. Results: Treatment with the B2R agonist preserved the spatial memory of transgenic mice and decreased amyloid plaque deposition. In organotypic hippocampal culture, treatment with B2R agonist decreased cell death, neuroinflammation, and S100B levels, and increased BDNF release. Conclusions: Our results indicate that the kallikrein–kinin system plays a beneficial role in Alzheimer’s disease through B2R activation. The use of B2R agonists could, therefore, be a possible therapeutic option for patients diagnosed with Alzheimer’s disease. |
format | Online Article Text |
id | pubmed-7601323 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76013232020-11-01 Kinin B2 Receptor Activation Prevents the Evolution of Alzheimer’s Disease Pathological Characteristics in a Transgenic Mouse Model Nunes, Marielza Andrade Toricelli, Mariana Schöwe, Natalia Mendes Malerba, Helena Nascimento Dong-Creste, Karis Ester Farah, Daniela Moura Azevedo Tuma De Angelis, Katia Irigoyen, Maria Claudia Gobeil, Fernand Araujo Viel, Tânia Buck, Hudson Sousa Pharmaceuticals (Basel) Article Background: Alzheimer’s disease is mainly characterized by remarkable neurodegeneration in brain areas related to memory formation. This progressive neurodegeneration causes cognitive impairment, changes in behavior, functional disability, and even death. Our group has demonstrated changes in the kallikrein–kinin system (KKS) in Alzheimer’s disease (AD) experimental models, but there is a lack of evidence about the role of the KKS in Alzheimer’s disease. Aim: In order to answer this question, we evaluated the potential of the kinin B2 receptors (BKB2R) to modify AD characteristics, particularly memory impairment, neurodegeneration, and Aβ peptide deposition. Methods: To assess the effects of B2, we used transgenic Alzheimer’s disease mice treated with B2 receptor (B2R) agonists and antagonists, and performed behavioral and biochemical tests. In addition, we performed organotypic hippocampal culture of wild-type (WT) and transgenic (TG) animals, where the density of cytokines, neurotrophin BDNF, activated astrocyte marker S100B, and cell death were analyzed after treatments. Results: Treatment with the B2R agonist preserved the spatial memory of transgenic mice and decreased amyloid plaque deposition. In organotypic hippocampal culture, treatment with B2R agonist decreased cell death, neuroinflammation, and S100B levels, and increased BDNF release. Conclusions: Our results indicate that the kallikrein–kinin system plays a beneficial role in Alzheimer’s disease through B2R activation. The use of B2R agonists could, therefore, be a possible therapeutic option for patients diagnosed with Alzheimer’s disease. MDPI 2020-10-01 /pmc/articles/PMC7601323/ /pubmed/33019732 http://dx.doi.org/10.3390/ph13100288 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nunes, Marielza Andrade Toricelli, Mariana Schöwe, Natalia Mendes Malerba, Helena Nascimento Dong-Creste, Karis Ester Farah, Daniela Moura Azevedo Tuma De Angelis, Katia Irigoyen, Maria Claudia Gobeil, Fernand Araujo Viel, Tânia Buck, Hudson Sousa Kinin B2 Receptor Activation Prevents the Evolution of Alzheimer’s Disease Pathological Characteristics in a Transgenic Mouse Model |
title | Kinin B2 Receptor Activation Prevents the Evolution of Alzheimer’s Disease Pathological Characteristics in a Transgenic Mouse Model |
title_full | Kinin B2 Receptor Activation Prevents the Evolution of Alzheimer’s Disease Pathological Characteristics in a Transgenic Mouse Model |
title_fullStr | Kinin B2 Receptor Activation Prevents the Evolution of Alzheimer’s Disease Pathological Characteristics in a Transgenic Mouse Model |
title_full_unstemmed | Kinin B2 Receptor Activation Prevents the Evolution of Alzheimer’s Disease Pathological Characteristics in a Transgenic Mouse Model |
title_short | Kinin B2 Receptor Activation Prevents the Evolution of Alzheimer’s Disease Pathological Characteristics in a Transgenic Mouse Model |
title_sort | kinin b2 receptor activation prevents the evolution of alzheimer’s disease pathological characteristics in a transgenic mouse model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601323/ https://www.ncbi.nlm.nih.gov/pubmed/33019732 http://dx.doi.org/10.3390/ph13100288 |
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