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Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer’s disease in metabolically stressed APPswe/PS1dE9 mice
BACKGROUND: Several studies stablished a relationship between metabolic disturbances and Alzheimer´s disease (AD) where inflammation plays a pivotal role. However, mechanisms involved still remain unclear. In the present study, we aimed to evaluate central and peripheral effects of dexibuprofen (DXI...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296685/ https://www.ncbi.nlm.nih.gov/pubmed/34294142 http://dx.doi.org/10.1186/s13578-021-00646-w |
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author | Ettcheto, Miren Sánchez-Lopez, Elena Cano, Amanda Carrasco, Marina Herrera, Katherine Manzine, Patricia R. Espinosa-Jimenez, Triana Busquets, Oriol Verdaguer, Ester Olloquequi, Jordi Auladell, Carme Folch, Jaume Camins, Antoni |
author_facet | Ettcheto, Miren Sánchez-Lopez, Elena Cano, Amanda Carrasco, Marina Herrera, Katherine Manzine, Patricia R. Espinosa-Jimenez, Triana Busquets, Oriol Verdaguer, Ester Olloquequi, Jordi Auladell, Carme Folch, Jaume Camins, Antoni |
author_sort | Ettcheto, Miren |
collection | PubMed |
description | BACKGROUND: Several studies stablished a relationship between metabolic disturbances and Alzheimer´s disease (AD) where inflammation plays a pivotal role. However, mechanisms involved still remain unclear. In the present study, we aimed to evaluate central and peripheral effects of dexibuprofen (DXI) in the progression of AD in APPswe/PS1dE9 (APP/PS1) female mice, a familial AD model, fed with high fat diet (HFD). Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice, at 6 months. Moreover, mice were divided into subgroups to which were administered drinking water or water supplemented with DXI (20 mg kg(−1) d(−1)) for 3 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-ITT) were performed to evaluate peripheral parameters and also behavioral tests to determine cognitive decline. Moreover, molecular studies such as Western blot and RT-PCR were carried out in liver to confirm metabolic effects and in hippocampus to analyze several pathways considered hallmarks in AD. RESULTS: Our studies demonstrate that DXI improved metabolic alterations observed in transgenic animals fed with HFD in vivo, data in accordance with those obtained at molecular level. Moreover, an improvement of cognitive decline and neuroinflammation among other alterations associated with AD were observed such as beta-amyloid plaque accumulation and unfolded protein response. CONCLUSIONS: Collectively, evidence suggest that chronic administration of DXI prevents the progression of AD through the regulation of inflammation which contribute to improve hallmarks of this pathology. Thus, this compound could constitute a novel therapeutic approach in the treatment of AD in a combined therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-021-00646-w. |
format | Online Article Text |
id | pubmed-8296685 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-82966852021-07-22 Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer’s disease in metabolically stressed APPswe/PS1dE9 mice Ettcheto, Miren Sánchez-Lopez, Elena Cano, Amanda Carrasco, Marina Herrera, Katherine Manzine, Patricia R. Espinosa-Jimenez, Triana Busquets, Oriol Verdaguer, Ester Olloquequi, Jordi Auladell, Carme Folch, Jaume Camins, Antoni Cell Biosci Research BACKGROUND: Several studies stablished a relationship between metabolic disturbances and Alzheimer´s disease (AD) where inflammation plays a pivotal role. However, mechanisms involved still remain unclear. In the present study, we aimed to evaluate central and peripheral effects of dexibuprofen (DXI) in the progression of AD in APPswe/PS1dE9 (APP/PS1) female mice, a familial AD model, fed with high fat diet (HFD). Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice, at 6 months. Moreover, mice were divided into subgroups to which were administered drinking water or water supplemented with DXI (20 mg kg(−1) d(−1)) for 3 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-ITT) were performed to evaluate peripheral parameters and also behavioral tests to determine cognitive decline. Moreover, molecular studies such as Western blot and RT-PCR were carried out in liver to confirm metabolic effects and in hippocampus to analyze several pathways considered hallmarks in AD. RESULTS: Our studies demonstrate that DXI improved metabolic alterations observed in transgenic animals fed with HFD in vivo, data in accordance with those obtained at molecular level. Moreover, an improvement of cognitive decline and neuroinflammation among other alterations associated with AD were observed such as beta-amyloid plaque accumulation and unfolded protein response. CONCLUSIONS: Collectively, evidence suggest that chronic administration of DXI prevents the progression of AD through the regulation of inflammation which contribute to improve hallmarks of this pathology. Thus, this compound could constitute a novel therapeutic approach in the treatment of AD in a combined therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-021-00646-w. BioMed Central 2021-07-22 /pmc/articles/PMC8296685/ /pubmed/34294142 http://dx.doi.org/10.1186/s13578-021-00646-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Ettcheto, Miren Sánchez-Lopez, Elena Cano, Amanda Carrasco, Marina Herrera, Katherine Manzine, Patricia R. Espinosa-Jimenez, Triana Busquets, Oriol Verdaguer, Ester Olloquequi, Jordi Auladell, Carme Folch, Jaume Camins, Antoni Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer’s disease in metabolically stressed APPswe/PS1dE9 mice |
title | Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer’s disease in metabolically stressed APPswe/PS1dE9 mice |
title_full | Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer’s disease in metabolically stressed APPswe/PS1dE9 mice |
title_fullStr | Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer’s disease in metabolically stressed APPswe/PS1dE9 mice |
title_full_unstemmed | Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer’s disease in metabolically stressed APPswe/PS1dE9 mice |
title_short | Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer’s disease in metabolically stressed APPswe/PS1dE9 mice |
title_sort | dexibuprofen ameliorates peripheral and central risk factors associated with alzheimer’s disease in metabolically stressed appswe/ps1de9 mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296685/ https://www.ncbi.nlm.nih.gov/pubmed/34294142 http://dx.doi.org/10.1186/s13578-021-00646-w |
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