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Title: | Dietary Sargassum fusiforme improves memory and reduces amyloid plaque load in an Alzheimer’s disease mouse model | Authors: | BOGIE, Jeroen HOEKS, Cindy SCHEPERS, Melissa TIANE, Assia CUYPERS, Ann Leijten, Frank Chintapakorn, Yupyn Suttiyut, Thiti Pornpakakul, Surachai Struik, Dicky Kerksiek, Anja Liu, Hong-Bing HELLINGS, Niels Martinez-Martinez, Pilar Jonker, Johan W. DEWACHTER, Ilse Sijbrands, Eric Walter, Jochen HENDRIKS, Jerome Groen, Albert Staels, Bart Lutjohann, Dieter VANMIERLO, Tim Mulder, Monique |
Issue Date: | 2019 | Source: | Scientific reports (Nature Publishing Group), 9 (Art N° 4908) | Abstract: | Activation of liver X receptors (LXRs) by synthetic agonists was found to improve cognition in Alzheimer’s disease (AD) mice. However, these LXR agonists induce hypertriglyceridemia and hepatic steatosis, hampering their use in the clinic. We hypothesized that phytosterols as LXR agonists enhance cognition in AD without affecting plasma and hepatic triglycerides. Phytosterols previously reported to activate LXRs were tested in a luciferase-based LXR reporter assay. Using this assay, we found that phytosterols commonly present in a Western type diet in physiological concentrations do not activate LXRs. However, a lipid extract of the 24(S)-Saringosterol-containing seaweed Sargassum fusiforme did potently activate LXRβ. Dietary supplementation of crude Sargassum fusiforme or a Sargassum fusiforme-derived lipid extract to AD mice significantly improved short-term memory and reduced hippocampal Aβ plaque load by 81%. Notably, none of the side effects typically induced by full synthetic LXR agonists were observed. In contrast, administration of the synthetic LXRα activator, AZ876, did not improve cognition and resulted in the accumulation of lipid droplets in the liver. Administration of Sargassum fusiforme-derived 24(S)-Saringosterol to cultured neurons reduced the secretion of Aβ42. Moreover, conditioned medium from 24(S)-Saringosterol-treated astrocytes added to microglia increased phagocytosis of Aβ. Our data show that Sargassum fusiforme improves cognition and alleviates AD pathology. This may be explained at least partly by 24(S)-Saringosterol-mediated LXRβ activation. | Notes: | Vanmierlo, T (reprint author), Hasselt Univ, Biomed Res Inst, Dept Immunol & Biochem, Martelarenlaan 42, B-3500 Hasselt, Belgium. Maastricht Univ, Sch Mental Hlth & Neurosci, Univ Singel 50, NL-6229 ER Maastricht, Netherlands. tim.vanmierlo@uhasselt.be | Document URI: | http://hdl.handle.net/1942/28164 | Link to publication/dataset: | https://www.ncbi.nlm.nih.gov/pubmed/30894635 | ISSN: | 2045-2322 | e-ISSN: | 2045-2322 | DOI: | 10.1038/s41598-019-41399-4 | ISI #: | 000461762600025 | Rights: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2020 |
Appears in Collections: | Research publications |
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Bogie Hoeks 2019 Dietary Sargassum fusiforme improves memory and reduces amyloid plaque load in an Alzheimers disease mouse model.pdf | Published version | 3.37 MB | Adobe PDF | View/Open |
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