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 (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Garrit, Anna (Universitat Autònoma de Barcelona. Departament de Ciències Morfològiques)
Reig-Vilallonga, Josep (Universitat Autònoma de Barcelona. Departament de Ciències Morfològiques)
Gimenez-Llort, Lydia (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Universitat Autònoma de Barcelona. Institut de Neurociències

Fecha:	2023
Resumen:	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.
Ayudas:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR-1468 European Commission. Horizon 2020 737390
Nota:	Altres ajuts: Memorial Mercedes Llort Sender, 2021/80/09241941.8; Universitat Autònoma de Barcelona, UAB-GE-260408
Derechos:	Aquest 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.
Lengua:	Anglès
Documento:	Article ; recerca
Materia:	Alzheimer's disease ; 3xTg-AD ; Liver-brain axis ; Obesity ; HPA axis ; Corticosterone ; Oxidative stress ; Social isolation ; Amyloidosis ; Steatosis
Publicado en:	Cells, Vol. 12 (may 2023) , ISSN 2073-4409

DOI: 10.3390/cells12111517
PMID: 37296638

20 p, 4.0 MB

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