Dietary Sargassum fusiforme improves memory and reduces amyloid plaque load in an Alzheimer’s disease mouse model View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Jeroen Bogie, Cindy Hoeks, Melissa Schepers, Assia Tiane, Ann Cuypers, Frank Leijten, Yupyn Chintapakorn, Thiti Suttiyut, Surachai Pornpakakul, Dicky Struik, Anja Kerksiek, Hong-Bing Liu, Niels Hellings, Pilar Martinez-Martinez, Johan W. Jonker, Ilse Dewachter, Eric Sijbrands, Jochen Walter, Jerome Hendriks, Albert Groen, Bart Staels, Dieter Lütjohann, Tim Vanmierlo, Monique Mulder

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. More... »

PAGES

4908

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-019-41399-4

DOI

http://dx.doi.org/10.1038/s41598-019-41399-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112872850

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30894635


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