Microglial Activation in the Retina of a Triple-Transgenic Alzheimer's Disease Mouse Model (3xTg-AD)

Bibliographic Details
Main Author: Salobrar-García, Elena
Publication Date: 2020
Other Authors: Rodrigues-Neves, Ana C., Ramírez, Ana I., de Hoz, Rosa, Fernández-Albarral, José A., López-Cuenca, Inés, Ramírez, José M., Ambrósio, António F., Salazar, Juan J.
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: https://hdl.handle.net/10316/106197
https://doi.org/10.3390/ijms21030816
Summary: Alzheimer's disease (AD) is the most common type of dementia in the world. The main biomarkers associated with AD are protein amyloid-β (Aβ) plaques and protein tau neurofibrillary tangles, which are responsible for brain neuroinflammation mediated by microglial cells. Increasing evidence has shown that the retina can also be affected in AD, presenting some molecular and cellular changes in the brain, such as microglia activation. However, there are only a few studies assessing such changes in the retinal microglia in animal models of AD. These studies use retinal sections, which have some limitations. In this study, we performed, for the first time in a triple-transgenic AD mouse model (3xTg-AD), a quantitative morphometric analysis of microglia activation (using the anti-Iba-1 antibody) in retinal whole-mounts, allowing visualization of the entire microglial cell, as well as its localization along the extension of the retina in different layers. Compared to age-matched animals, the retina of 3xTg-AD mice presents a higher number of microglial cells and a thicker microglial cell body area. Moreover, the microglia migrate, reorient, and retract their processes, changing their localization from a parallel to a perpendicular position relative to the retinal surface. These findings demonstrate clear microglia remodeling in the retina of 3xTg-AD mice.
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spelling Microglial Activation in the Retina of a Triple-Transgenic Alzheimer's Disease Mouse Model (3xTg-AD)Alzheimer’s diseaseretinaneuroinflammationmicrogliatriple transgenic Alzheimer’s disease mouse model3xTg-ADmorphometric analysisAlzheimer's disease (AD) is the most common type of dementia in the world. The main biomarkers associated with AD are protein amyloid-β (Aβ) plaques and protein tau neurofibrillary tangles, which are responsible for brain neuroinflammation mediated by microglial cells. Increasing evidence has shown that the retina can also be affected in AD, presenting some molecular and cellular changes in the brain, such as microglia activation. However, there are only a few studies assessing such changes in the retinal microglia in animal models of AD. These studies use retinal sections, which have some limitations. In this study, we performed, for the first time in a triple-transgenic AD mouse model (3xTg-AD), a quantitative morphometric analysis of microglia activation (using the anti-Iba-1 antibody) in retinal whole-mounts, allowing visualization of the entire microglial cell, as well as its localization along the extension of the retina in different layers. Compared to age-matched animals, the retina of 3xTg-AD mice presents a higher number of microglial cells and a thicker microglial cell body area. Moreover, the microglia migrate, reorient, and retract their processes, changing their localization from a parallel to a perpendicular position relative to the retinal surface. These findings demonstrate clear microglia remodeling in the retina of 3xTg-AD mice.This research was funded by the Santa Casa Mantero Belard Award 2015 (MB-1049-2015), FCT (SFRH/BD/52045/2012, SFRH/BPD/93672/2013, PEst UID/NEU/04539/2013 and UID/NEU/04539/2019), COMPETE-FEDER (POCI-01-0145-FEDER-007440 and POCI-01-0145-FEDER-016428), and Centro 2020 Regional Operational Programme (CENTRO-01-0145-FEDER-000008: BrainHealth); and Ophthalmological Network OFTARED (RD16/0008/0005 of the Institute of Health of Carlos III of the Spanish Ministry of Economy; by the PN I+D+i 2008–2011, by the ISCIII-Subdirección General de Redes y Centros de Investigación Cooperativa, and by the European program FEDER; and SAF-2014-53779-R: from the Spanish Ministry of Economy and Competitiveness. And the E.S.-G.APC was funded by a Predoctoral Fellowship (FPU13/01910) from the Spanish Ministry of Education, Culture and Sport, and Fellowship (EST16/00024) for a stay in a foreign institution of the MECD of the Spanish government at the Coimbra Institute for Biomedical and Clinical Research (iCBR), University of Coimbra, Portugal; and J.A.F.-A. is currently funded by a Predoctoral Fellowship (FPU17/01023) from the Spanish Ministry of Science, Innovation, and Universities; and I.L.-C. is currently funded by a Predoctoral Fellowship (CT42/18-CT43/18) from the Complutense University of Madrid.MDPI2020-01-27info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://hdl.handle.net/10316/106197https://hdl.handle.net/10316/106197https://doi.org/10.3390/ijms21030816eng1422-0067320126761422-0067Salobrar-García, ElenaRodrigues-Neves, Ana C.Ramírez, Ana I.de Hoz, RosaFernández-Albarral, José A.López-Cuenca, InésRamírez, José M.Ambrósio, António F.Salazar, Juan J.info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2023-04-06T10:19:50Zoai:estudogeral.uc.pt:10316/106197Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T05:56:37.471820Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Microglial Activation in the Retina of a Triple-Transgenic Alzheimer's Disease Mouse Model (3xTg-AD)
title Microglial Activation in the Retina of a Triple-Transgenic Alzheimer's Disease Mouse Model (3xTg-AD)
spellingShingle Microglial Activation in the Retina of a Triple-Transgenic Alzheimer's Disease Mouse Model (3xTg-AD)
Salobrar-García, Elena
Alzheimer’s disease
retina
neuroinflammation
microglia
triple transgenic Alzheimer’s disease mouse model
3xTg-AD
morphometric analysis
title_short Microglial Activation in the Retina of a Triple-Transgenic Alzheimer's Disease Mouse Model (3xTg-AD)
title_full Microglial Activation in the Retina of a Triple-Transgenic Alzheimer's Disease Mouse Model (3xTg-AD)
title_fullStr Microglial Activation in the Retina of a Triple-Transgenic Alzheimer's Disease Mouse Model (3xTg-AD)
title_full_unstemmed Microglial Activation in the Retina of a Triple-Transgenic Alzheimer's Disease Mouse Model (3xTg-AD)
title_sort Microglial Activation in the Retina of a Triple-Transgenic Alzheimer's Disease Mouse Model (3xTg-AD)
author Salobrar-García, Elena
author_facet Salobrar-García, Elena
Rodrigues-Neves, Ana C.
Ramírez, Ana I.
de Hoz, Rosa
Fernández-Albarral, José A.
López-Cuenca, Inés
Ramírez, José M.
Ambrósio, António F.
Salazar, Juan J.
author_role author
author2 Rodrigues-Neves, Ana C.
Ramírez, Ana I.
de Hoz, Rosa
Fernández-Albarral, José A.
López-Cuenca, Inés
Ramírez, José M.
Ambrósio, António F.
Salazar, Juan J.
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Salobrar-García, Elena
Rodrigues-Neves, Ana C.
Ramírez, Ana I.
de Hoz, Rosa
Fernández-Albarral, José A.
López-Cuenca, Inés
Ramírez, José M.
Ambrósio, António F.
Salazar, Juan J.
dc.subject.por.fl_str_mv Alzheimer’s disease
retina
neuroinflammation
microglia
triple transgenic Alzheimer’s disease mouse model
3xTg-AD
morphometric analysis
topic Alzheimer’s disease
retina
neuroinflammation
microglia
triple transgenic Alzheimer’s disease mouse model
3xTg-AD
morphometric analysis
description Alzheimer's disease (AD) is the most common type of dementia in the world. The main biomarkers associated with AD are protein amyloid-β (Aβ) plaques and protein tau neurofibrillary tangles, which are responsible for brain neuroinflammation mediated by microglial cells. Increasing evidence has shown that the retina can also be affected in AD, presenting some molecular and cellular changes in the brain, such as microglia activation. However, there are only a few studies assessing such changes in the retinal microglia in animal models of AD. These studies use retinal sections, which have some limitations. In this study, we performed, for the first time in a triple-transgenic AD mouse model (3xTg-AD), a quantitative morphometric analysis of microglia activation (using the anti-Iba-1 antibody) in retinal whole-mounts, allowing visualization of the entire microglial cell, as well as its localization along the extension of the retina in different layers. Compared to age-matched animals, the retina of 3xTg-AD mice presents a higher number of microglial cells and a thicker microglial cell body area. Moreover, the microglia migrate, reorient, and retract their processes, changing their localization from a parallel to a perpendicular position relative to the retinal surface. These findings demonstrate clear microglia remodeling in the retina of 3xTg-AD mice.
publishDate 2020
dc.date.none.fl_str_mv 2020-01-27
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.uri.fl_str_mv https://hdl.handle.net/10316/106197
https://hdl.handle.net/10316/106197
https://doi.org/10.3390/ijms21030816
url https://hdl.handle.net/10316/106197
https://doi.org/10.3390/ijms21030816
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dc.publisher.none.fl_str_mv MDPI
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