Altered Clock Gene Expression in Female APP/PS1 Mice and Aquaporin-Dependent Amyloid Accumulation in the Retina

Alzheimer's disease (AD), the most prevalent form of dementia, is a neurodegenerative disorder characterized by different pathological symptomatology, including disrupted circadian rhythm. The regulation of circadian rhythm depends on the light information that is projected from the retina to t...

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Autores: Carrero, Laura, Antequera, Desireé, Alcalde, Ignacio, Megías, Diego, Ordóñez-Gutiérrez, Lara, Gutierrez, Cristina, Merayo-Lloves, Jesús, Wandosell, Francisco, Municio, Cristina, Carro, Eva
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/16845
Acceso en línea:http://hdl.handle.net/20.500.12105/16845
Access Level:acceso abierto
Palabra clave:Amyloid beta-Protein Precursor
Alzheimer Disease
Mice
Humans
Female
Animals
Infant
Amyloid beta-Peptides
Mice, Transgenic
Retina
Aquaporin 4
Gene Expression
Disease Models, Animal
Presenilin-1
Plaque, Amyloid
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/16845
network_acronym_str ES
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repository_id_str
spelling Altered Clock Gene Expression in Female APP/PS1 Mice and Aquaporin-Dependent Amyloid Accumulation in the RetinaCarrero, LauraAntequera, DesireéAlcalde, IgnacioMegías, DiegoOrdóñez-Gutiérrez, LaraGutierrez, CristinaMerayo-Lloves, JesúsWandosell, FranciscoMunicio, CristinaCarro, EvaAmyloid beta-Protein PrecursorAlzheimer DiseaseMiceHumansFemaleAnimalsInfantAmyloid beta-PeptidesMice, TransgenicRetinaAquaporin 4Gene ExpressionDisease Models, AnimalPresenilin-1Plaque, AmyloidAlzheimer's disease (AD), the most prevalent form of dementia, is a neurodegenerative disorder characterized by different pathological symptomatology, including disrupted circadian rhythm. The regulation of circadian rhythm depends on the light information that is projected from the retina to the suprachiasmatic nucleus in the hypothalamus. Studies of AD patients and AD transgenic mice have revealed AD retinal pathology, including amyloid-β (Aβ) accumulation that can directly interfere with the regulation of the circadian cycle. Although the cause of AD pathology is poorly understood, one of the main risk factors for AD is female gender. Here, we found that female APP/PS1 mice at 6- and 12-months old display severe circadian rhythm disturbances and retinal pathological hallmarks, including Aβ deposits in retinal layers. Since brain Aβ transport is facilitated by aquaporin (AQP)4, the expression of AQPs were also explored in APP/PS1 retina to investigate a potential correlation between retinal Aβ deposits and AQPs expression. Important reductions in AQP1, AQP4, and AQP5 were detected in the retinal tissue of these transgenic mice, mainly at 6-months of age. Taken together, our findings suggest that abnormal transport of Aβ, mediated by impaired AQPs expression, contributes to the retinal degeneration in the early stages of AD.Multidisciplinary Digital Publishing Institute (MDPI)Instituto de Salud Carlos IIIUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Centro de Investigación Biomédica en Red - CIBERNED (Enfermedades Neurodegenerativas)Ministerio de Ciencia e Innovación (España)20232023-12-1920232023-10-2720232023-10-27research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/20.500.12105/16845reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/168452026-06-12T12:43:37Z
dc.title.none.fl_str_mv Altered Clock Gene Expression in Female APP/PS1 Mice and Aquaporin-Dependent Amyloid Accumulation in the Retina
title Altered Clock Gene Expression in Female APP/PS1 Mice and Aquaporin-Dependent Amyloid Accumulation in the Retina
spellingShingle Altered Clock Gene Expression in Female APP/PS1 Mice and Aquaporin-Dependent Amyloid Accumulation in the Retina
Carrero, Laura
Amyloid beta-Protein Precursor
Alzheimer Disease
Mice
Humans
Female
Animals
Infant
Amyloid beta-Peptides
Mice, Transgenic
Retina
Aquaporin 4
Gene Expression
Disease Models, Animal
Presenilin-1
Plaque, Amyloid
title_short Altered Clock Gene Expression in Female APP/PS1 Mice and Aquaporin-Dependent Amyloid Accumulation in the Retina
title_full Altered Clock Gene Expression in Female APP/PS1 Mice and Aquaporin-Dependent Amyloid Accumulation in the Retina
title_fullStr Altered Clock Gene Expression in Female APP/PS1 Mice and Aquaporin-Dependent Amyloid Accumulation in the Retina
title_full_unstemmed Altered Clock Gene Expression in Female APP/PS1 Mice and Aquaporin-Dependent Amyloid Accumulation in the Retina
title_sort Altered Clock Gene Expression in Female APP/PS1 Mice and Aquaporin-Dependent Amyloid Accumulation in the Retina
dc.creator.none.fl_str_mv Carrero, Laura
Antequera, Desireé
Alcalde, Ignacio
Megías, Diego
Ordóñez-Gutiérrez, Lara
Gutierrez, Cristina
Merayo-Lloves, Jesús
Wandosell, Francisco
Municio, Cristina
Carro, Eva
author Carrero, Laura
author_facet Carrero, Laura
Antequera, Desireé
Alcalde, Ignacio
Megías, Diego
Ordóñez-Gutiérrez, Lara
Gutierrez, Cristina
Merayo-Lloves, Jesús
Wandosell, Francisco
Municio, Cristina
Carro, Eva
author_role author
author2 Antequera, Desireé
Alcalde, Ignacio
Megías, Diego
Ordóñez-Gutiérrez, Lara
Gutierrez, Cristina
Merayo-Lloves, Jesús
Wandosell, Francisco
Municio, Cristina
Carro, Eva
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Centro de Investigación Biomédica en Red - CIBERNED (Enfermedades Neurodegenerativas)
Ministerio de Ciencia e Innovación (España)
dc.subject.none.fl_str_mv Amyloid beta-Protein Precursor
Alzheimer Disease
Mice
Humans
Female
Animals
Infant
Amyloid beta-Peptides
Mice, Transgenic
Retina
Aquaporin 4
Gene Expression
Disease Models, Animal
Presenilin-1
Plaque, Amyloid
topic Amyloid beta-Protein Precursor
Alzheimer Disease
Mice
Humans
Female
Animals
Infant
Amyloid beta-Peptides
Mice, Transgenic
Retina
Aquaporin 4
Gene Expression
Disease Models, Animal
Presenilin-1
Plaque, Amyloid
description Alzheimer's disease (AD), the most prevalent form of dementia, is a neurodegenerative disorder characterized by different pathological symptomatology, including disrupted circadian rhythm. The regulation of circadian rhythm depends on the light information that is projected from the retina to the suprachiasmatic nucleus in the hypothalamus. Studies of AD patients and AD transgenic mice have revealed AD retinal pathology, including amyloid-β (Aβ) accumulation that can directly interfere with the regulation of the circadian cycle. Although the cause of AD pathology is poorly understood, one of the main risk factors for AD is female gender. Here, we found that female APP/PS1 mice at 6- and 12-months old display severe circadian rhythm disturbances and retinal pathological hallmarks, including Aβ deposits in retinal layers. Since brain Aβ transport is facilitated by aquaporin (AQP)4, the expression of AQPs were also explored in APP/PS1 retina to investigate a potential correlation between retinal Aβ deposits and AQPs expression. Important reductions in AQP1, AQP4, and AQP5 were detected in the retinal tissue of these transgenic mice, mainly at 6-months of age. Taken together, our findings suggest that abnormal transport of Aβ, mediated by impaired AQPs expression, contributes to the retinal degeneration in the early stages of AD.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-12-19
2023
2023-10-27
2023
2023-10-27
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/16845
url http://hdl.handle.net/20.500.12105/16845
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute (MDPI)
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute (MDPI)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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