Dietary Sargassum fusiforme improves memory and reduces amyloid plaque load in an Alzheimer's disease mouse model

被引：64

作者：

Bogie, Jeroen ^{[1
]}

Hoeks, Cindy ^{[1
]}

Schepers, Melissa ^{[1
,9
]}

Tiane, Assia ^{[1
,9
]}

Cuypers, Ann ^{[2
]}

Leijten, Frank ^{[3
]}

Chintapakorn, Yupyn ^{[4
]}

Suttiyut, Thiti ^{[4
]}

Pornpakakul, Surachai ^{[5
]}

Struik, Dicky ^{[6
]}

Kerksiek, Anja ^{[7
]}

Liu, Hong-Bing ^{[8
]}

Hellings, Niels ^{[1
]}

Martinez-Martinez, Pilar ^{[9
]}

Jonker, Johan W. ^{[6
]}

Dewachter, Ilse ^{[1
]}

Sijbrands, Eric ^{[3
]}

Walter, Jochen ^{[10
]}

Hendriks, Jerome ^{[1
]}

Groen, Albert ^{[11
]}

Staels, Bart ^{[12
]}

Luetjohann, Dieter ^{[7
]}

Vanmierlo, Tim ^{[1
,9
]}

Mulder, Monique ^{[3
]}

机构：

[1] Hasselt Univ, Biomed Res Inst, Dept Immunol & Biochem, Martelarenlaan 42, B-3500 Hasselt, Belgium

[2] Hasselt Univ, Ctr Environm Sci, Martelarenlaan 42, B-3500 Hasselt, Belgium

[3] Erasmus MC, Dept Internal Med, Lab Vasc Med, Wytemaweg 80, NL-3015 CN Rotterdam, Netherlands

[4] Chulalongkorn Univ, Fac Sci, Ctr Excellence Environm & Plant Physiol, Dept Bot, Bangkok 10330, Thailand

[5] Chulalongkorn Univ, Fac Sci, Dept Chem, Bangkok 10330, Thailand

[6] Univ Groningen, Univ Med Ctr Groningen, Dept Pediat, Sect Mol Metab & Nutr, Hanzepl 1, NL-9713 GZ Groningen, Netherlands

[7] Inst Clin Chem & Clin Pharmacol, Sigmund Freud Str 25, D-53127 Bonn, Germany

[8] Ocean Univ China, Sch Med & Pharm, Key Lab Marine Drugs, Minist Educ, Yushan Rd 5, Qingdao 266003, Peoples R China

[9] Maastricht Univ, Sch Mental Hlth & Neurosci, Univ Singel 50, NL-6229 ER Maastricht, Netherlands

[10] Univ Bonn, Dept Neurol Mol Cell Biol, Sigmund Freud Str 25, D-53127 Bonn, Germany

[11] Univ Amsterdam, Acad Med Ctr, Dept Med Biochem, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

[12] Univ Lille, Inserm, Univ Hosp CHU, EGID,U1011,Inst Pasteur Lille, F-59019 Lille, France

来源：

SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期

关键词：

LIVER-X RECEPTORS; LXR AGONIST TO901317; HUMAN SERUM-ALBUMIN; PLANT STEROLS; CHOLESTEROL HOMEOSTASIS; BETA-SITOSTEROL; BRAIN; MICE; METABOLISM; ACTIVATION;

D O I：

10.1038/s41598-019-41399-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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 LXR beta. Dietary supplementation of crude Sargassum fusiforme or a Sargassum fusiforme-derived lipid extract to AD mice significantly improved short-term memory and reduced hippocampal A beta 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 LXRa 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 A beta 42. Moreover, conditioned medium from 24(S)-Saringosterol-treated astrocytes added to microglia increased phagocytosis of A beta. Our data show that Sargassum fusiforme improves cognition and alleviates AD pathology. This may be explained at least partly by 24(S)-Saringosterol-mediated LXR beta activation.

引用

页数：16

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