Role of Retinoid X Receptors (RXRs) and dietary vitamin A in Alzheimer's disease: Evidence from clinicopathological and preclinical studies

Background: Vitamin A (VitA), via its active metabolite retinoic acid (RA), is critical for the maintenance of memory function with advancing age. Although its role in Alzheimer's disease (AD) is not well understood, data suggest that impaired brain VitA signaling is associated with the accumul...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Essi F. Biyong, Cyntia Tremblay, Manon Leclerc, Vicky Caron, Serge Alfos, Jean-Christophe Helbling, Léa Rodriguez, Vincent Pernet, David A. Bennett, Véronique Pallet, Frédéric Calon
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Alzheimer's disease Vitamin A Aging Amyloid Prevention Diet Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/f5fc3723625a42ecb80950e796769d61
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f5fc3723625a42ecb80950e796769d61
record_format	dspace
spelling	oai:doaj.org-article:f5fc3723625a42ecb80950e796769d612021-12-04T04:33:09ZRole of Retinoid X Receptors (RXRs) and dietary vitamin A in Alzheimer's disease: Evidence from clinicopathological and preclinical studies1095-953X10.1016/j.nbd.2021.105542https://doaj.org/article/f5fc3723625a42ecb80950e796769d612021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0969996121002916https://doaj.org/toc/1095-953XBackground: Vitamin A (VitA), via its active metabolite retinoic acid (RA), is critical for the maintenance of memory function with advancing age. Although its role in Alzheimer's disease (AD) is not well understood, data suggest that impaired brain VitA signaling is associated with the accumulation of β-amyloid peptides (Aβ), and could thus contribute to the onset of AD. Methods: We evaluated the protective action of a six-month-long dietary VitA-supplementation (20 IU/g), starting at 8 months of age, on the memory and the neuropathology of the 3xTg-AD mouse model of AD (n = 11-14/group; including 4–6 females and 7–8 males). We also measured protein levels of Retinoic Acid Receptor β (RARβ) and Retinoid X Receptor γ (RXRγ) in homogenates from the inferior parietal cortex of 60 participants of the Religious Orders study (ROS) divided in three groups: no cognitive impairment (NCI) (n = 20), mild cognitive impairment (MCI) (n = 20) and AD (n = 20). Results: The VitA-enriched diet preserved spatial memory of 3xTg-AD mice in the Y maze. VitA-supplementation affected hippocampal RXR expression in an opposite way according to sex by tending to increase in males and decrease in females their mRNA expression. VitA-enriched diet also reduced the amount of hippocampal Aβ40 and Aβ42, as well as the phosphorylation of tau protein at sites Ser396/Ser404 (PHF-1) in males. VitA-supplementation had no effect on tau phosphorylation in females but worsened their hippocampal Aβ load. However, the expression of Rxr-β in the hippocampus was negatively correlated with the amount of both soluble and insoluble Aβ in both males and females.Western immunoblotting in the human cortical samples of the ROS study did not reveal differences in RARβ levels. However, it evidenced a switch from a 60-kDa-RXRγ to a 55-kDa-RXRγ in AD, correlating with ante mortem cognitive decline and the accumulation of neuritic plaques in the brain cortex. Conclusion: Our data suggest that (i) an altered expression of RXRs receptors is a contributor to β-amyloid pathology in both humans and 3xTg-AD mice, (ii) a chronic exposure of 3xTg-AD mice to a VitA-enriched diet may be protective in males, but not in females.Essi F. BiyongCyntia TremblayManon LeclercVicky CaronSerge AlfosJean-Christophe HelblingLéa RodriguezVincent PernetDavid A. BennettVéronique PalletFrédéric CalonElsevierarticleAlzheimer's diseaseVitamin AAgingAmyloidPreventionDietNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENNeurobiology of Disease, Vol 161, Iss , Pp 105542- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer's disease Vitamin A Aging Amyloid Prevention Diet Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Alzheimer's disease Vitamin A Aging Amyloid Prevention Diet Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Essi F. Biyong Cyntia Tremblay Manon Leclerc Vicky Caron Serge Alfos Jean-Christophe Helbling Léa Rodriguez Vincent Pernet David A. Bennett Véronique Pallet Frédéric Calon Role of Retinoid X Receptors (RXRs) and dietary vitamin A in Alzheimer's disease: Evidence from clinicopathological and preclinical studies
description	Background: Vitamin A (VitA), via its active metabolite retinoic acid (RA), is critical for the maintenance of memory function with advancing age. Although its role in Alzheimer's disease (AD) is not well understood, data suggest that impaired brain VitA signaling is associated with the accumulation of β-amyloid peptides (Aβ), and could thus contribute to the onset of AD. Methods: We evaluated the protective action of a six-month-long dietary VitA-supplementation (20 IU/g), starting at 8 months of age, on the memory and the neuropathology of the 3xTg-AD mouse model of AD (n = 11-14/group; including 4–6 females and 7–8 males). We also measured protein levels of Retinoic Acid Receptor β (RARβ) and Retinoid X Receptor γ (RXRγ) in homogenates from the inferior parietal cortex of 60 participants of the Religious Orders study (ROS) divided in three groups: no cognitive impairment (NCI) (n = 20), mild cognitive impairment (MCI) (n = 20) and AD (n = 20). Results: The VitA-enriched diet preserved spatial memory of 3xTg-AD mice in the Y maze. VitA-supplementation affected hippocampal RXR expression in an opposite way according to sex by tending to increase in males and decrease in females their mRNA expression. VitA-enriched diet also reduced the amount of hippocampal Aβ40 and Aβ42, as well as the phosphorylation of tau protein at sites Ser396/Ser404 (PHF-1) in males. VitA-supplementation had no effect on tau phosphorylation in females but worsened their hippocampal Aβ load. However, the expression of Rxr-β in the hippocampus was negatively correlated with the amount of both soluble and insoluble Aβ in both males and females.Western immunoblotting in the human cortical samples of the ROS study did not reveal differences in RARβ levels. However, it evidenced a switch from a 60-kDa-RXRγ to a 55-kDa-RXRγ in AD, correlating with ante mortem cognitive decline and the accumulation of neuritic plaques in the brain cortex. Conclusion: Our data suggest that (i) an altered expression of RXRs receptors is a contributor to β-amyloid pathology in both humans and 3xTg-AD mice, (ii) a chronic exposure of 3xTg-AD mice to a VitA-enriched diet may be protective in males, but not in females.
format	article
author	Essi F. Biyong Cyntia Tremblay Manon Leclerc Vicky Caron Serge Alfos Jean-Christophe Helbling Léa Rodriguez Vincent Pernet David A. Bennett Véronique Pallet Frédéric Calon
author_facet	Essi F. Biyong Cyntia Tremblay Manon Leclerc Vicky Caron Serge Alfos Jean-Christophe Helbling Léa Rodriguez Vincent Pernet David A. Bennett Véronique Pallet Frédéric Calon
author_sort	Essi F. Biyong
title	Role of Retinoid X Receptors (RXRs) and dietary vitamin A in Alzheimer's disease: Evidence from clinicopathological and preclinical studies
title_short	Role of Retinoid X Receptors (RXRs) and dietary vitamin A in Alzheimer's disease: Evidence from clinicopathological and preclinical studies
title_full	Role of Retinoid X Receptors (RXRs) and dietary vitamin A in Alzheimer's disease: Evidence from clinicopathological and preclinical studies
title_fullStr	Role of Retinoid X Receptors (RXRs) and dietary vitamin A in Alzheimer's disease: Evidence from clinicopathological and preclinical studies
title_full_unstemmed	Role of Retinoid X Receptors (RXRs) and dietary vitamin A in Alzheimer's disease: Evidence from clinicopathological and preclinical studies
title_sort	role of retinoid x receptors (rxrs) and dietary vitamin a in alzheimer's disease: evidence from clinicopathological and preclinical studies
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/f5fc3723625a42ecb80950e796769d61
work_keys_str_mv	AT essifbiyong roleofretinoidxreceptorsrxrsanddietaryvitaminainalzheimersdiseaseevidencefromclinicopathologicalandpreclinicalstudies AT cyntiatremblay roleofretinoidxreceptorsrxrsanddietaryvitaminainalzheimersdiseaseevidencefromclinicopathologicalandpreclinicalstudies AT manonleclerc roleofretinoidxreceptorsrxrsanddietaryvitaminainalzheimersdiseaseevidencefromclinicopathologicalandpreclinicalstudies AT vickycaron roleofretinoidxreceptorsrxrsanddietaryvitaminainalzheimersdiseaseevidencefromclinicopathologicalandpreclinicalstudies AT sergealfos roleofretinoidxreceptorsrxrsanddietaryvitaminainalzheimersdiseaseevidencefromclinicopathologicalandpreclinicalstudies AT jeanchristophehelbling roleofretinoidxreceptorsrxrsanddietaryvitaminainalzheimersdiseaseevidencefromclinicopathologicalandpreclinicalstudies AT learodriguez roleofretinoidxreceptorsrxrsanddietaryvitaminainalzheimersdiseaseevidencefromclinicopathologicalandpreclinicalstudies AT vincentpernet roleofretinoidxreceptorsrxrsanddietaryvitaminainalzheimersdiseaseevidencefromclinicopathologicalandpreclinicalstudies AT davidabennett roleofretinoidxreceptorsrxrsanddietaryvitaminainalzheimersdiseaseevidencefromclinicopathologicalandpreclinicalstudies AT veroniquepallet roleofretinoidxreceptorsrxrsanddietaryvitaminainalzheimersdiseaseevidencefromclinicopathologicalandpreclinicalstudies AT fredericcalon roleofretinoidxreceptorsrxrsanddietaryvitaminainalzheimersdiseaseevidencefromclinicopathologicalandpreclinicalstudies
_version_	1718373066374905856

Role of Retinoid X Receptors (RXRs) and dietary vitamin A in Alzheimer's disease: Evidence from clinicopathological and preclinical studies

Ejemplares similares