• LOGIN
Repository logo

BORIS Portal

Bern Open Repository and Information System

  • Publication
  • Projects
  • Funding
  • Research Data
  • Organizations
  • Researchers
  • LOGIN
Repository logo
Unibern.ch
  1. Home
  2. Publications
  3. Role of Retinoid X Receptors (RXRs) and dietary vitamin A in Alzheimer's disease: Evidence from clinicopathological and preclinical studies.
 

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

Options
  • Details
BORIS DOI
10.48350/165972
Date of Publication
December 2021
Publication Type
Article
Division/Institute

Universitätsklinik fü...

Author
Biyong, Essi F
Tremblay, Cyntia
Leclerc, Manon
Caron, Vicky
Alfos, Serge
Helbling, Jean-Christophe
Rodriguez, Léa
Pernet, Vincent
Universitätsklinik für Neurologie
Bennett, David A
Pallet, Véronique
Calon, Frédéric
Subject(s)

600 - Technology::610...

Series
Neurobiology of disease
ISSN or ISBN (if monograph)
0969-9961
Publisher
Elsevier
Language
English
Publisher DOI
10.1016/j.nbd.2021.105542
PubMed ID
34737043
Uncontrolled Keywords

3xTg-AD mouse Aging A...

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.
Handle
https://boris-portal.unibe.ch/handle/20.500.12422/67789
Show full item
File(s)
FileFile TypeFormatSizeLicensePublisher/Copright statementContent
Byiong__2021__Role_of_Retinoid_X_Receptors.pdftextAdobe PDF9.09 MBpublishedOpen
BORIS Portal
Bern Open Repository and Information System
Build: 360c85 [14.04. 8:05]
Explore
  • Projects
  • Funding
  • Publications
  • Research Data
  • Organizations
  • Researchers
More
  • About BORIS Portal
  • Send Feedback
  • Cookie settings
  • Service Policy
Follow us on
  • Mastodon
  • YouTube
  • LinkedIn
UniBe logo