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

N. Martens, M. Schepers, N. Zhan, F. Leijten, G. Voortman, A. Tiane, B. Rombaut, J. Poisquet, N. van de Sande, A. Kerksiek, F. Kuipers, J.W. Jonker, H.B. Liu, D. Lutjohann, T. Vanmierlo, M.T. Mulder*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

We recently found that dietary supplementation with the seaweed Sargassum fusiforme, containing the preferential LXR beta-agonist 24(S)-saringosterol, prevented memory decline and reduced amyloid-beta (A beta) 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 APPswePS1 Delta E9 mice and wildtype C57BL/6J littermates received 24(S)-saringosterol (0.5 mg/25 g body weight/day) (APPswePS1 Delta E9 n = 20; C57BL/6J n = 19) or vehicle (APPswePS1 Delta E9 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, A beta 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 APPswePS1 Delta E9 mice without affecting the A beta plaque load. Moreover, 24(S)-saringosterol prevented the increase in the inflammatory marker Iba1 in the cortex of APPswePS1 Delta E9 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 APPswePS1 Delta E9 mice independent of effects on A beta 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.
Original languageEnglish
Article number190
Number of pages17
JournalMarine Drugs
Volume19
Issue number4
DOIs
Publication statusPublished - 1 Apr 2021

Keywords

  • Alzheimer&#8217
  • s disease
  • seaweed
  • Sargassum fusiforme
  • phytosterols
  • cholesterol metabolism
  • X-RECEPTOR ACTIVATION
  • SARGASSUM-FUSIFORME
  • APOLIPOPROTEIN-E
  • IMPROVES MEMORY
  • BROWN-ALGAE
  • CHOLESTEROL
  • BRAIN
  • STEROLS
  • POLYSACCHARIDE
  • INFLAMMATION

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