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

Nikita Martens, Melissa Schepers, Na Zhan, Frank Leijten, Gardi Voortman, Assia Tiane, Ben Rombaut, Janne Poisquet, Nienke van de Sande, Anja Kerksiek, Folkert Kuipers, Johan W Jonker, Hongbing Liu, Dieter Lütjohann, Tim Vanmierlo, Monique T Mulder*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

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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.

Originele taal-2English
Artikelnummer190
Aantal pagina's17
TijdschriftMarine Drugs
Volume19
Nummer van het tijdschrift4
DOI's
StatusPublished - apr-2021

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