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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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