Salivary Lactoferrin Expression in a Mouse Model of Alzheimer’s Disease

In the last few years, microbial infection and innate immune theories have been proposed as an alternative approach explaining the etiopathogenesis and origin of Alzheimer's disease (AD). Lactoferrin, one of the main antimicrobial proteins in saliva, is an important modulator of immune response...

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Autores: Antequera, Desiree, Moneo, Diego, Carrero, Laura, Bartolome, Fernando, Ferrer, Isidro, Proctor, Gordon, Carro, Eva
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/180957
Acceso en línea:https://hdl.handle.net/2445/180957
Access Level:acceso abierto
Palabra clave:Ferro en l'organisme
Malaltia d'Alzheimer
Iron in the body
Alzheimer's disease
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spelling Salivary Lactoferrin Expression in a Mouse Model of Alzheimer’s DiseaseAntequera, DesireeMoneo, DiegoCarrero, LauraBartolome, FernandoFerrer, IsidroProctor, GordonCarro, EvaFerro en l'organismeMalaltia d'AlzheimerIron in the bodyAlzheimer's diseaseIn the last few years, microbial infection and innate immune theories have been proposed as an alternative approach explaining the etiopathogenesis and origin of Alzheimer's disease (AD). Lactoferrin, one of the main antimicrobial proteins in saliva, is an important modulator of immune response and inflammation, and represents an important defensive element by inducing a broad spectrum of antimicrobial effects against microbial infections. We demonstrated that lactoferrin levels in saliva are decreased in prodromal and dementia stages of AD compared with healthy subjects. That finding seems to be specific to cerebral amyloid-β (Aβ) load as such observation was not observed in healthy elderly controls or those subjects with frontotemporal dementia. In the present study, we analysed salivary lactoferrin levels in a mouse model of AD. We observed robust and early reduction of lactoferrin levels in saliva from 6- and 12-month-old APP/PS1 mice. Because saliva is secreted by salivary glands, we presume that deregulation in salivary glands resulting in reduced salivary lactoferrin levels may occur in AD. To test this hypothesis, we collected submandibular glands from APP/PS1 mice, as well as submandibular gland tissue from AD patients and we analysed the expression levels of key components of the salivary protein signalling pathway. A significant reduction in M3 receptor levels was found along with decreased acetylcholine (Ach) levels in submandibular glands from APP/PS1 mice. Similarly, a reduction in M3 receptor levels was observed in human submandibular glands from AD patients but in that case, the Ach levels were found increased. Our data suggest that the ACh-mediated M3 signalling pathway is impaired in salivary glands in AD, resulting in salivary gland dysfunction and reduced salivary lactoferrin secretion.Frontiers Media SA2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/180957Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3389/fimmu.2021.749468Frontiers in Immunology, 2021, vol. 12https://doi.org/10.3389/fimmu.2021.749468cc by (c) Antequera, Desiree et al, 2021http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1809572026-05-27T06:46:51Z
dc.title.none.fl_str_mv Salivary Lactoferrin Expression in a Mouse Model of Alzheimer’s Disease
title Salivary Lactoferrin Expression in a Mouse Model of Alzheimer’s Disease
spellingShingle Salivary Lactoferrin Expression in a Mouse Model of Alzheimer’s Disease
Antequera, Desiree
Ferro en l'organisme
Malaltia d'Alzheimer
Iron in the body
Alzheimer's disease
title_short Salivary Lactoferrin Expression in a Mouse Model of Alzheimer’s Disease
title_full Salivary Lactoferrin Expression in a Mouse Model of Alzheimer’s Disease
title_fullStr Salivary Lactoferrin Expression in a Mouse Model of Alzheimer’s Disease
title_full_unstemmed Salivary Lactoferrin Expression in a Mouse Model of Alzheimer’s Disease
title_sort Salivary Lactoferrin Expression in a Mouse Model of Alzheimer’s Disease
dc.creator.none.fl_str_mv Antequera, Desiree
Moneo, Diego
Carrero, Laura
Bartolome, Fernando
Ferrer, Isidro
Proctor, Gordon
Carro, Eva
author Antequera, Desiree
author_facet Antequera, Desiree
Moneo, Diego
Carrero, Laura
Bartolome, Fernando
Ferrer, Isidro
Proctor, Gordon
Carro, Eva
author_role author
author2 Moneo, Diego
Carrero, Laura
Bartolome, Fernando
Ferrer, Isidro
Proctor, Gordon
Carro, Eva
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Ferro en l'organisme
Malaltia d'Alzheimer
Iron in the body
Alzheimer's disease
topic Ferro en l'organisme
Malaltia d'Alzheimer
Iron in the body
Alzheimer's disease
description In the last few years, microbial infection and innate immune theories have been proposed as an alternative approach explaining the etiopathogenesis and origin of Alzheimer's disease (AD). Lactoferrin, one of the main antimicrobial proteins in saliva, is an important modulator of immune response and inflammation, and represents an important defensive element by inducing a broad spectrum of antimicrobial effects against microbial infections. We demonstrated that lactoferrin levels in saliva are decreased in prodromal and dementia stages of AD compared with healthy subjects. That finding seems to be specific to cerebral amyloid-β (Aβ) load as such observation was not observed in healthy elderly controls or those subjects with frontotemporal dementia. In the present study, we analysed salivary lactoferrin levels in a mouse model of AD. We observed robust and early reduction of lactoferrin levels in saliva from 6- and 12-month-old APP/PS1 mice. Because saliva is secreted by salivary glands, we presume that deregulation in salivary glands resulting in reduced salivary lactoferrin levels may occur in AD. To test this hypothesis, we collected submandibular glands from APP/PS1 mice, as well as submandibular gland tissue from AD patients and we analysed the expression levels of key components of the salivary protein signalling pathway. A significant reduction in M3 receptor levels was found along with decreased acetylcholine (Ach) levels in submandibular glands from APP/PS1 mice. Similarly, a reduction in M3 receptor levels was observed in human submandibular glands from AD patients but in that case, the Ach levels were found increased. Our data suggest that the ACh-mediated M3 signalling pathway is impaired in salivary glands in AD, resulting in salivary gland dysfunction and reduced salivary lactoferrin secretion.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/180957
url https://hdl.handle.net/2445/180957
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2021.749468
Frontiers in Immunology, 2021, vol. 12
https://doi.org/10.3389/fimmu.2021.749468
dc.rights.none.fl_str_mv cc by (c) Antequera, Desiree et al, 2021
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Antequera, Desiree et al, 2021
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media SA
publisher.none.fl_str_mv Frontiers Media SA
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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