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 |   |
| 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.
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| 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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