Hepatic Oxi-Inflammation and Neophobia as Potential Liver-Brain Axis Targets for Alzheimer's Disease and Aging, with Strong Sensitivity to Sex, Isolation, and Obesity

Research on Alzheimer's disease (AD) has classically focused on alterations that occur in the brain and their intra- and extracellular neuropathological hallmarks. However, the oxiinflammation hypothesis of aging may also play a role in neuroimmunoendocrine dysregulation and the disease's...

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Autores: Fraile Ramos, Juan|||0000-0002-4475-4360, Garrit, Anna, Reig Vilallonga, Josep, Gimenez-Llort, Lydia|||0000-0002-4091-489X
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:282476
Acceso en línea:https://ddd.uab.cat/record/282476
https://dx.doi.org/urn:doi:10.3390/cells12111517
Access Level:acceso abierto
Palabra clave:Alzheimer's disease
3xTg-AD
Liver-brain axis
Obesity
HPA axis
Corticosterone
Oxidative stress
Social isolation
Amyloidosis
Steatosis
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spelling Hepatic Oxi-Inflammation and Neophobia as Potential Liver-Brain Axis Targets for Alzheimer's Disease and Aging, with Strong Sensitivity to Sex, Isolation, and ObesityFraile Ramos, Juan|||0000-0002-4475-4360Garrit, AnnaReig Vilallonga, JosepGimenez-Llort, Lydia|||0000-0002-4091-489XAlzheimer's disease3xTg-ADLiver-brain axisObesityHPA axisCorticosteroneOxidative stressSocial isolationAmyloidosisSteatosisResearch on Alzheimer's disease (AD) has classically focused on alterations that occur in the brain and their intra- and extracellular neuropathological hallmarks. However, the oxiinflammation hypothesis of aging may also play a role in neuroimmunoendocrine dysregulation and the disease's pathophysiology, where the liver emerges as a target organ due to its implication in regulating metabolism and supporting the immune system. In the present work, we demonstrate organ (hepatomegaly), tissue (histopathological amyloidosis), and cellular oxidative stress (decreased glutathione peroxidase and increased glutathione reductase enzymatic activities) and inflammation (increased IL-6 and TNFα) as hallmarks of hepatic dysfunction in 16-month-old male and female 3xTgAD mice at advanced stages of the disease, and as compared to age- and sex-matched non-transgenic (NTg) counterparts. Moreover, liver-brain axis alterations were found through behavioral (increased neophobia) and HPA axis correlations that were enhanced under forced isolation. In all cases, sex (male) and isolation (naturalistic and forced) were determinants of worse hepatomegaly, oxidative stress, and inflammation progression. In addition, obesity in old male NTg mice was translated into a worse steatosis grade. Further research is underway determine whether these alterations could correlate with a worse disease prognosis and to establish potential integrative system targets for AD research.Universitat Autònoma de Barcelona. Institut de Neurociències 22023-01-0120232023-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/282476https://dx.doi.org/urn:doi:10.3390/cells12111517reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-1468European Commission https://doi.org/10.13039/501100000780 737390open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2824762026-06-06T12:50:31Z
dc.title.none.fl_str_mv Hepatic Oxi-Inflammation and Neophobia as Potential Liver-Brain Axis Targets for Alzheimer's Disease and Aging, with Strong Sensitivity to Sex, Isolation, and Obesity
title Hepatic Oxi-Inflammation and Neophobia as Potential Liver-Brain Axis Targets for Alzheimer's Disease and Aging, with Strong Sensitivity to Sex, Isolation, and Obesity
spellingShingle Hepatic Oxi-Inflammation and Neophobia as Potential Liver-Brain Axis Targets for Alzheimer's Disease and Aging, with Strong Sensitivity to Sex, Isolation, and Obesity
Fraile Ramos, Juan|||0000-0002-4475-4360
Alzheimer's disease
3xTg-AD
Liver-brain axis
Obesity
HPA axis
Corticosterone
Oxidative stress
Social isolation
Amyloidosis
Steatosis
title_short Hepatic Oxi-Inflammation and Neophobia as Potential Liver-Brain Axis Targets for Alzheimer's Disease and Aging, with Strong Sensitivity to Sex, Isolation, and Obesity
title_full Hepatic Oxi-Inflammation and Neophobia as Potential Liver-Brain Axis Targets for Alzheimer's Disease and Aging, with Strong Sensitivity to Sex, Isolation, and Obesity
title_fullStr Hepatic Oxi-Inflammation and Neophobia as Potential Liver-Brain Axis Targets for Alzheimer's Disease and Aging, with Strong Sensitivity to Sex, Isolation, and Obesity
title_full_unstemmed Hepatic Oxi-Inflammation and Neophobia as Potential Liver-Brain Axis Targets for Alzheimer's Disease and Aging, with Strong Sensitivity to Sex, Isolation, and Obesity
title_sort Hepatic Oxi-Inflammation and Neophobia as Potential Liver-Brain Axis Targets for Alzheimer's Disease and Aging, with Strong Sensitivity to Sex, Isolation, and Obesity
dc.creator.none.fl_str_mv Fraile Ramos, Juan|||0000-0002-4475-4360
Garrit, Anna
Reig Vilallonga, Josep
Gimenez-Llort, Lydia|||0000-0002-4091-489X
author Fraile Ramos, Juan|||0000-0002-4475-4360
author_facet Fraile Ramos, Juan|||0000-0002-4475-4360
Garrit, Anna
Reig Vilallonga, Josep
Gimenez-Llort, Lydia|||0000-0002-4091-489X
author_role author
author2 Garrit, Anna
Reig Vilallonga, Josep
Gimenez-Llort, Lydia|||0000-0002-4091-489X
author2_role author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona. Institut de Neurociències
dc.subject.none.fl_str_mv Alzheimer's disease
3xTg-AD
Liver-brain axis
Obesity
HPA axis
Corticosterone
Oxidative stress
Social isolation
Amyloidosis
Steatosis
topic Alzheimer's disease
3xTg-AD
Liver-brain axis
Obesity
HPA axis
Corticosterone
Oxidative stress
Social isolation
Amyloidosis
Steatosis
description Research on Alzheimer's disease (AD) has classically focused on alterations that occur in the brain and their intra- and extracellular neuropathological hallmarks. However, the oxiinflammation hypothesis of aging may also play a role in neuroimmunoendocrine dysregulation and the disease's pathophysiology, where the liver emerges as a target organ due to its implication in regulating metabolism and supporting the immune system. In the present work, we demonstrate organ (hepatomegaly), tissue (histopathological amyloidosis), and cellular oxidative stress (decreased glutathione peroxidase and increased glutathione reductase enzymatic activities) and inflammation (increased IL-6 and TNFα) as hallmarks of hepatic dysfunction in 16-month-old male and female 3xTgAD mice at advanced stages of the disease, and as compared to age- and sex-matched non-transgenic (NTg) counterparts. Moreover, liver-brain axis alterations were found through behavioral (increased neophobia) and HPA axis correlations that were enhanced under forced isolation. In all cases, sex (male) and isolation (naturalistic and forced) were determinants of worse hepatomegaly, oxidative stress, and inflammation progression. In addition, obesity in old male NTg mice was translated into a worse steatosis grade. Further research is underway determine whether these alterations could correlate with a worse disease prognosis and to establish potential integrative system targets for AD research.
publishDate 2023
dc.date.none.fl_str_mv 2
2023-01-01
2023
2023-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
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 https://ddd.uab.cat/record/282476
https://dx.doi.org/urn:doi:10.3390/cells12111517
url https://ddd.uab.cat/record/282476
https://dx.doi.org/urn:doi:10.3390/cells12111517
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-1468
European Commission https://doi.org/10.13039/501100000780 737390
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://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
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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