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24(S)-Saringosterol Prevents Cognitive Decline in a Mouse Model for Alzheimer’s Disease

We recently found that dietary supplementation with the seaweed Sargassum fusiforme, containing the preferential LXRβ-agonist 24(S)-saringosterol, prevented memory decline and reduced amyloid-β (Aβ) deposition in an Alzheimer’s disease (AD) mouse model without inducing hepatic steatosis. Here, we ex...

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Autores principales: Martens, Nikita, Schepers, Melissa, Zhan, Na, Leijten, Frank, Voortman, Gardi, Tiane, Assia, Rombaut, Ben, Poisquet, Janne, van de Sande, Nienke, Kerksiek, Anja, Kuipers, Folkert, Jonker, Johan W., Liu, Hongbing, Lütjohann, Dieter, Vanmierlo, Tim, Mulder, Monique T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065937/
https://www.ncbi.nlm.nih.gov/pubmed/33801706
http://dx.doi.org/10.3390/md19040190
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author Martens, Nikita
Schepers, Melissa
Zhan, Na
Leijten, Frank
Voortman, Gardi
Tiane, Assia
Rombaut, Ben
Poisquet, Janne
van de Sande, Nienke
Kerksiek, Anja
Kuipers, Folkert
Jonker, Johan W.
Liu, Hongbing
Lütjohann, Dieter
Vanmierlo, Tim
Mulder, Monique T.
author_facet Martens, Nikita
Schepers, Melissa
Zhan, Na
Leijten, Frank
Voortman, Gardi
Tiane, Assia
Rombaut, Ben
Poisquet, Janne
van de Sande, Nienke
Kerksiek, Anja
Kuipers, Folkert
Jonker, Johan W.
Liu, Hongbing
Lütjohann, Dieter
Vanmierlo, Tim
Mulder, Monique T.
author_sort Martens, Nikita
collection PubMed
description We recently found that dietary supplementation with the seaweed Sargassum fusiforme, containing the preferential LXRβ-agonist 24(S)-saringosterol, prevented memory decline and reduced amyloid-β (Aβ) deposition in an Alzheimer’s disease (AD) mouse model without inducing hepatic steatosis. Here, we examined the effects of 24(S)-saringosterol as a food additive on cognition and neuropathology in AD mice. Six-month-old male APPswePS1ΔE9 mice and wildtype C57BL/6J littermates received 24(S)-saringosterol (0.5 mg/25 g body weight/day) (APPswePS1ΔE9 n = 20; C57BL/6J n = 19) or vehicle (APPswePS1ΔE9 n = 17; C57BL/6J n = 19) for 10 weeks. Cognition was assessed using object recognition and object location tasks. Sterols were analyzed by gas chromatography/mass spectrometry, Aβ and inflammatory markers by immunohistochemistry, and gene expression by quantitative real-time PCR. Hepatic lipids were quantified after Oil-Red-O staining. Administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice without affecting the Aβ plaque load. Moreover, 24(S)-saringosterol prevented the increase in the inflammatory marker Iba1 in the cortex of APPswePS1ΔE9 mice (p < 0.001). Furthermore, 24(S)-saringosterol did not affect the expression of lipid metabolism-related LXR-response genes in the hippocampus nor the hepatic neutral lipid content. Thus, administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice independent of effects on Aβ load and without adverse effects on liver fat content. The anti-inflammatory effects of 24(S)-saringosterol may contribute to the prevention of cognitive decline.
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spelling pubmed-80659372021-04-25 24(S)-Saringosterol Prevents Cognitive Decline in a Mouse Model for Alzheimer’s Disease Martens, Nikita Schepers, Melissa Zhan, Na Leijten, Frank Voortman, Gardi Tiane, Assia Rombaut, Ben Poisquet, Janne van de Sande, Nienke Kerksiek, Anja Kuipers, Folkert Jonker, Johan W. Liu, Hongbing Lütjohann, Dieter Vanmierlo, Tim Mulder, Monique T. Mar Drugs Article We recently found that dietary supplementation with the seaweed Sargassum fusiforme, containing the preferential LXRβ-agonist 24(S)-saringosterol, prevented memory decline and reduced amyloid-β (Aβ) deposition in an Alzheimer’s disease (AD) mouse model without inducing hepatic steatosis. Here, we examined the effects of 24(S)-saringosterol as a food additive on cognition and neuropathology in AD mice. Six-month-old male APPswePS1ΔE9 mice and wildtype C57BL/6J littermates received 24(S)-saringosterol (0.5 mg/25 g body weight/day) (APPswePS1ΔE9 n = 20; C57BL/6J n = 19) or vehicle (APPswePS1ΔE9 n = 17; C57BL/6J n = 19) for 10 weeks. Cognition was assessed using object recognition and object location tasks. Sterols were analyzed by gas chromatography/mass spectrometry, Aβ and inflammatory markers by immunohistochemistry, and gene expression by quantitative real-time PCR. Hepatic lipids were quantified after Oil-Red-O staining. Administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice without affecting the Aβ plaque load. Moreover, 24(S)-saringosterol prevented the increase in the inflammatory marker Iba1 in the cortex of APPswePS1ΔE9 mice (p < 0.001). Furthermore, 24(S)-saringosterol did not affect the expression of lipid metabolism-related LXR-response genes in the hippocampus nor the hepatic neutral lipid content. Thus, administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice independent of effects on Aβ load and without adverse effects on liver fat content. The anti-inflammatory effects of 24(S)-saringosterol may contribute to the prevention of cognitive decline. MDPI 2021-03-27 /pmc/articles/PMC8065937/ /pubmed/33801706 http://dx.doi.org/10.3390/md19040190 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Martens, Nikita
Schepers, Melissa
Zhan, Na
Leijten, Frank
Voortman, Gardi
Tiane, Assia
Rombaut, Ben
Poisquet, Janne
van de Sande, Nienke
Kerksiek, Anja
Kuipers, Folkert
Jonker, Johan W.
Liu, Hongbing
Lütjohann, Dieter
Vanmierlo, Tim
Mulder, Monique T.
24(S)-Saringosterol Prevents Cognitive Decline in a Mouse Model for Alzheimer’s Disease
title 24(S)-Saringosterol Prevents Cognitive Decline in a Mouse Model for Alzheimer’s Disease
title_full 24(S)-Saringosterol Prevents Cognitive Decline in a Mouse Model for Alzheimer’s Disease
title_fullStr 24(S)-Saringosterol Prevents Cognitive Decline in a Mouse Model for Alzheimer’s Disease
title_full_unstemmed 24(S)-Saringosterol Prevents Cognitive Decline in a Mouse Model for Alzheimer’s Disease
title_short 24(S)-Saringosterol Prevents Cognitive Decline in a Mouse Model for Alzheimer’s Disease
title_sort 24(s)-saringosterol prevents cognitive decline in a mouse model for alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065937/
https://www.ncbi.nlm.nih.gov/pubmed/33801706
http://dx.doi.org/10.3390/md19040190
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