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...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-12-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996121002916 |
| _version_ | 1818721880244224000 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T20:45:45Z |
| format | Article |
| id | doaj.art-f5fc3723625a42ecb80950e796769d61 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T20:45:45Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
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| series | Neurobiology of Disease |
| spelling | doaj.art-f5fc3723625a42ecb80950e796769d612022-12-21T21:33:10ZengElsevierNeurobiology of Disease1095-953X2021-12-01161105542Role of Retinoid X Receptors (RXRs) and dietary vitamin A in Alzheimer's disease: Evidence from clinicopathological and preclinical studiesEssi F. Biyong0Cyntia Tremblay1Manon Leclerc2Vicky Caron3Serge Alfos4Jean-Christophe Helbling5Léa Rodriguez6Vincent Pernet7David A. Bennett8Véronique Pallet9Frédéric Calon10Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000 Bordeaux, France; Faculté de pharmacie, Université Laval, Québec, Québec, Canada; Centre de recherche du CHU de Québec-Université Laval (CHUL), Axe Neurosciences, 2705 Boulevard Laurier, Québec, Québec, Canada; Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Québec, Québec, Canada; LIA OptiNutriBrain – Laboratoire International Associé (NutriNeuro France-INAF Canada), CanadaFaculté de pharmacie, Université Laval, Québec, Québec, Canada; Centre de recherche du CHU de Québec-Université Laval (CHUL), Axe Neurosciences, 2705 Boulevard Laurier, Québec, Québec, CanadaFaculté de pharmacie, Université Laval, Québec, Québec, Canada; Centre de recherche du CHU de Québec-Université Laval (CHUL), Axe Neurosciences, 2705 Boulevard Laurier, Québec, Québec, CanadaFaculté de pharmacie, Université Laval, Québec, Québec, Canada; Centre de recherche du CHU de Québec-Université Laval (CHUL), Axe Neurosciences, 2705 Boulevard Laurier, Québec, Québec, CanadaUniv. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000 Bordeaux, FranceUniv. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000 Bordeaux, FranceCUO-Recherche, Centre de Recherche du CHU de Québec, Québec, QC, Canada; Département d'ophtalmologie, Faculté de Médecine, Université Laval, Québec, QC, CanadaCUO-Recherche, Centre de Recherche du CHU de Québec, Québec, QC, Canada; Département d'ophtalmologie, Faculté de Médecine, Université Laval, Québec, QC, CanadaRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USAUniv. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000 Bordeaux, France; LIA OptiNutriBrain – Laboratoire International Associé (NutriNeuro France-INAF Canada), CanadaFaculté de pharmacie, Université Laval, Québec, Québec, Canada; Centre de recherche du CHU de Québec-Université Laval (CHUL), Axe Neurosciences, 2705 Boulevard Laurier, Québec, Québec, Canada; Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Québec, Québec, Canada; LIA OptiNutriBrain – Laboratoire International Associé (NutriNeuro France-INAF Canada), Canada; Corresponding author at: Centre de recherche du CHU de Québec-Université Laval (CHUL), Room T267, 2705 Boulevard Laurier, Québec, Québec, Canada, G1V 4G2.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.http://www.sciencedirect.com/science/article/pii/S0969996121002916Alzheimer's diseaseVitamin AAgingAmyloidPreventionDiet |
| spellingShingle | 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 Neurobiology of Disease Alzheimer's disease Vitamin A Aging Amyloid Prevention Diet |
| title | 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_short | 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 |
| topic | Alzheimer's disease Vitamin A Aging Amyloid Prevention Diet |
| url | http://www.sciencedirect.com/science/article/pii/S0969996121002916 |
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