Disturbed circadian rhythm and retinal degeneration in a mouse model of Alzheimer's disease

The circadian clock is synchronized to the 24 h day by environmental light which is transmitted from the retina to the suprachiasmatic nucleus (SCN) primarily via the retinohypothalamic tract (RHT). Circadian rhythm abnormalities have been reported in neurodegenerative disorders such as Alzheimer�...

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Autores: Carrero, Laura, Antequera, Desireé, Alcalde, Ignacio, Megías, Diego, Figueiro-Silva, Joana, Merayo-Lloves, Jesús, Municio, Cristina, Carro, Eva
Formato: artículo
Fecha de publicación:2023
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/16375
Acesso em linha:http://hdl.handle.net/20.500.12105/16375
Access Level:acceso abierto
Palavra-chave:Alzheimer Disease
Retinal Degeneration
Mice
Animals
Retina
Mice, Transgenic
Circadian Rhythm
Disease Models, Animal
Amyloid beta-Protein Precursor
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spelling Disturbed circadian rhythm and retinal degeneration in a mouse model of Alzheimer's diseaseCarrero, LauraAntequera, DesireéAlcalde, IgnacioMegías, DiegoFigueiro-Silva, JoanaMerayo-Lloves, JesúsMunicio, CristinaCarro, EvaAlzheimer DiseaseRetinal DegenerationMiceAnimalsRetinaMice, TransgenicCircadian RhythmDisease Models, AnimalAmyloid beta-Protein PrecursorThe circadian clock is synchronized to the 24 h day by environmental light which is transmitted from the retina to the suprachiasmatic nucleus (SCN) primarily via the retinohypothalamic tract (RHT). Circadian rhythm abnormalities have been reported in neurodegenerative disorders such as Alzheimer's disease (AD). Whether these AD-related changes are a result of the altered clock gene expression, retina degeneration, including the dysfunction in RHT transmission, loss of retinal ganglion cells and its electrophysiological capabilities, or a combination of all of these pathological mechanisms, is not known. Here, we evaluated transgenic APP/PS1 mouse model of AD and wild-type mice at 6- and 12-month-old, as early and late pathological stage, respectively. We noticed the alteration of circadian clock gene expression not only in the hypothalamus but also in two extra-hypothalamic brain regions, cerebral cortex and hippocampus, in APP/PS1 mice. These alterations were observed in 6-month-old transgenic mice and were exacerbated at 12 months of age. This could be explained by the reduced RHT projections in the SCN of APP/PS1 mice, correlating with downregulation of hypothalamic GABAergic response in APP/PS1 mice in advanced stage of pathology. Importantly, we also report retinal degeneration in APP/PS1 mice, including Aβ deposits and reduced choline acetyltransferase levels, loss of melanopsin retinal ganglion cells and functional integrity mainly of inner retina layers. Our findings support the theory that retinal degeneration constitutes an early pathological event that directly affects the control of circadian rhythm in AD.BioMed Central (BMC)Instituto de Salud Carlos IIIResearch Institute Hospital 12 de OctubreUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Centro de Investigación Biomédica en Red - CIBERNED (Enfermedades Neurodegenerativas)20232023-08-2920232023-03-3120232023-03-31research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/20.500.12105/16375reponame: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:20.500.12105/163752026-06-12T12:43:37Z
dc.title.none.fl_str_mv Disturbed circadian rhythm and retinal degeneration in a mouse model of Alzheimer's disease
title Disturbed circadian rhythm and retinal degeneration in a mouse model of Alzheimer's disease
spellingShingle Disturbed circadian rhythm and retinal degeneration in a mouse model of Alzheimer's disease
Carrero, Laura
Alzheimer Disease
Retinal Degeneration
Mice
Animals
Retina
Mice, Transgenic
Circadian Rhythm
Disease Models, Animal
Amyloid beta-Protein Precursor
title_short Disturbed circadian rhythm and retinal degeneration in a mouse model of Alzheimer's disease
title_full Disturbed circadian rhythm and retinal degeneration in a mouse model of Alzheimer's disease
title_fullStr Disturbed circadian rhythm and retinal degeneration in a mouse model of Alzheimer's disease
title_full_unstemmed Disturbed circadian rhythm and retinal degeneration in a mouse model of Alzheimer's disease
title_sort Disturbed circadian rhythm and retinal degeneration in a mouse model of Alzheimer's disease
dc.creator.none.fl_str_mv Carrero, Laura
Antequera, Desireé
Alcalde, Ignacio
Megías, Diego
Figueiro-Silva, Joana
Merayo-Lloves, Jesús
Municio, Cristina
Carro, Eva
author Carrero, Laura
author_facet Carrero, Laura
Antequera, Desireé
Alcalde, Ignacio
Megías, Diego
Figueiro-Silva, Joana
Merayo-Lloves, Jesús
Municio, Cristina
Carro, Eva
author_role author
author2 Antequera, Desireé
Alcalde, Ignacio
Megías, Diego
Figueiro-Silva, Joana
Merayo-Lloves, Jesús
Municio, Cristina
Carro, Eva
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Research Institute Hospital 12 de Octubre
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Centro de Investigación Biomédica en Red - CIBERNED (Enfermedades Neurodegenerativas)
dc.subject.none.fl_str_mv Alzheimer Disease
Retinal Degeneration
Mice
Animals
Retina
Mice, Transgenic
Circadian Rhythm
Disease Models, Animal
Amyloid beta-Protein Precursor
topic Alzheimer Disease
Retinal Degeneration
Mice
Animals
Retina
Mice, Transgenic
Circadian Rhythm
Disease Models, Animal
Amyloid beta-Protein Precursor
description The circadian clock is synchronized to the 24 h day by environmental light which is transmitted from the retina to the suprachiasmatic nucleus (SCN) primarily via the retinohypothalamic tract (RHT). Circadian rhythm abnormalities have been reported in neurodegenerative disorders such as Alzheimer's disease (AD). Whether these AD-related changes are a result of the altered clock gene expression, retina degeneration, including the dysfunction in RHT transmission, loss of retinal ganglion cells and its electrophysiological capabilities, or a combination of all of these pathological mechanisms, is not known. Here, we evaluated transgenic APP/PS1 mouse model of AD and wild-type mice at 6- and 12-month-old, as early and late pathological stage, respectively. We noticed the alteration of circadian clock gene expression not only in the hypothalamus but also in two extra-hypothalamic brain regions, cerebral cortex and hippocampus, in APP/PS1 mice. These alterations were observed in 6-month-old transgenic mice and were exacerbated at 12 months of age. This could be explained by the reduced RHT projections in the SCN of APP/PS1 mice, correlating with downregulation of hypothalamic GABAergic response in APP/PS1 mice in advanced stage of pathology. Importantly, we also report retinal degeneration in APP/PS1 mice, including Aβ deposits and reduced choline acetyltransferase levels, loss of melanopsin retinal ganglion cells and functional integrity mainly of inner retina layers. Our findings support the theory that retinal degeneration constitutes an early pathological event that directly affects the control of circadian rhythm in AD.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-08-29
2023
2023-03-31
2023
2023-03-31
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/20.500.12105/16375
url http://hdl.handle.net/20.500.12105/16375
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
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central (BMC)
publisher.none.fl_str_mv BioMed Central (BMC)
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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