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24(S)-saringosterol prevents cognitive decline in a mouse model for Alzheimer's disease
Martens, N.; Schepers, M.; Zhang, N.; Leijten, F.; Voortman, G.; Tiane, A.; Rombaut, B.; Poisquet, J.; van de Sande, N.; Kerksiek, A.; Kuipers, F.; Jonker, J.W.; Liu, H.; Lütjohann, D.; Vanmierlo, T.; Mulder, M.T. (2021). 24(S)-saringosterol prevents cognitive decline in a mouse model for Alzheimer's disease. Mar. Drugs 19(4): 190. https://dx.doi.org/10.3390/md19040190
In: Marine Drugs. Molecular Diversity Preservation International (MDPI): Basel. ISSN 1660-3397; e-ISSN 1660-3397, more
Peer reviewed article  

Available in  Authors 

Keywords
    Seaweed
    Sargassum fusiforme (Harvey) Setchell, 1931 [WoRMS]
    Marine/Coastal
Author keywords
    Alzheimer’s disease; seaweed; Sargassum fusiforme; phytosterols; cholesterol metabolism

Authors  Top 
  • Martens, N., more
  • Schepers, M., more
  • Zhang, N.
  • Leijten, F.
  • Voortman, G.
  • Tiane, A., more
  • Rombaut, B., more
  • Poisquet, J., more
  • van de Sande, N.
  • Kerksiek, A.
  • Kuipers, F.
  • Jonker, J.W.
  • Liu, H.
  • Lütjohann, D.
  • Vanmierlo, T., more
  • Mulder, M.T.

Abstract
    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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