title: Omega-3 polyunsaturated fatty acids promote amyloid-β clearance from the brain through mediating the function of the glymphatic system.
abstract: Impairment of amyloid-β (Aβ) clearance leads to Aβ accumulation in the brain during the development of Alzheimer's disease (AD). Strategies that can restore or improve the clearance function hold great promise in delaying or preventing the onset of AD. Here, we show that n-3 polyunsaturated fatty acids (PUFAs), by use of fat-1 transgenic mice and oral administration of fish oil, significantly promote interstitial Aβ clearance from the brain and resist Aβ injury. Such beneficial effects were abolished in Aqp4-knockout mice, suggesting that the AQP4-dependent glymphatic system is actively involved in the promoting the effects of n-3 PUFAs on the clearance of extracellular Aβ. Imaging on clarified brain tissues clearly displayed that n-3 PUFAs markedly inhibit the activation of astrocytes and protect the AQP4 polarization in the affected brain region after Aβ injection. The results of the present study prove a novel mechanism by which n-3 PUFAs exert protective roles in reducing Aβ accumulation via mediating the glymphatic system function.-Ren, H., Luo, C., Feng, Y., Yao, X., Shi, Z., Liang, F., Kang, J. X., Wan, J.-B., Pei, Z., Su, H. Omega-3 polyunsaturated fatty acids promote amyloid-β clearance from the brain through mediating the function of the glymphatic system.
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
authors: Huixia
authors: H
authors: Ren
authors: Department of Neurology, Second Clinical Medical College, Guangdong Medical University, Dongguan, China.
authors: Chuanming
authors: C
authors: Luo
authors: Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; and.
authors: Yanqing
authors: Y
authors: Feng
authors: Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; and.
authors: Xiaoli
authors: X
authors: Yao
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
authors: Zhe
authors: Z
authors: Shi
authors: Department of Neurology, Second Clinical Medical College, Guangdong Medical University, Dongguan, China.
authors: Fengyin
authors: F
authors: Liang
authors: Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors: Jing X
authors: JX
authors: Kang
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
authors: Jian-Bo
authors: JB
authors: Wan
authors: Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; and.
authors: Zhong
authors: Z
authors: Pei
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China; huanxingsu@umac.mo.
authors: Huanxing
authors: H
authors: Su
mesh_terms: D000284:Administration, Oral; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism; D001253:Astrocytes / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D016229:Amyloid beta-Peptides; D051401:Aquaporin 4; D015525:Fatty Acids, Omega-3
keywords: AQP4 polarization; DHA; extracellular solutes clearance; fish oil; perivascular pathways