Up-regulation of myelin-associated glycoprotein is associated with the ameliorating effect of omega-3 polyunsaturated fatty acids on Alzheimer's disease progression in APP-PS1 transgenic mice

  • Food Funct. 2024 Nov 11;15(22):11236-11251. doi: 10.1039/d4fo03355h.
Yan Shao  1  2 ,  Fei Li  2 ,  Bo Zou  3 ,  Yanling Jin  1 ,  Xiaoyang Wang  2 ,  Liting Wang  2 ,  Youying Huang  2 ,  Yu Xie  1 ,  Wei Sun  2 ,  Jing X Kang  4  5 ,  Kai Liu  6  7 ,  Yi Huang  2 ,  Wei Huang  2 ,  Bin Wang  3  8
Affiliations
  • 1. Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang 310014, China.
  • 2. Biomedical Analysis Center, Army Medical University, Chongqing 400038, China. [email protected].
  • 3. Department of Clinical Nutrition, Shenzhen Longgang Central Hospital, Shenzhen 518116, China. [email protected].
  • 4. Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
  • 5. Omega-3 and Global Health Institute, Boston, MA 02129, USA.
  • 6. Department of Endocrinology, General Hospital of Northern Theater Command, Shenyang 110016, P. R. China.
  • 7. Department of Disease Surveillance, Center for Disease Control and Prevention of Northern Theater Command, Shenyang 110034, P.R. China.
  • 8. Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Army Medical University, Chongqing 400038, China.
PMID: 39453315 DOI: 10.1039/d4fo03355h
Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive behavioral and cognitive impairments. Despite growing evidence of the neuroprotective action of omega-3 polyunsaturated fatty acids (PUFAs), the effects and mechanism of omega-3 PUFAs on AD control are yet to be clarified. By crossing male heterozygous fat-1 mice with female APP/PS1 mice, we assessed whether elevated tissue omega-3 PUFA levels could alleviate AD progression and their underlying mechanism among the offspring WT, APP/PS1 and APP/PS1 × fat-1 groups at various stages. We found that the fat-1 transgene significantly increased brain omega-3 PUFA and docosahexaenoic acid (DHA) levels, and cognitive deficits together with brain Aβ-40 and Aβ-42 levels in 6-month-old APP/PS1 × fat-1 mice were significantly lower than those in APP/PS1 mice. Subsequently, the tandem mass tag (TMT) method revealed the elevated expression of cortex and hippocampus myelin-associated glycoprotein (MAG) in APP/PS1 × fat-1 mice at 2-6 months. Furthermore, GO and KEGG pathway enrichment analysis suggested that the MAG-related myelin sheath pathway and its interaction with AD were regulated by omega-3 PUFAs. Moreover, subsequent western blot assays showed that both increased endogenous omega-3 levels and in vitro supplemented DHA up-regulated MAG expression, and the AD-protective effects of DHA on LPS-induced BV2 cells were significantly weakened when MAG was inhibited by si-RNA transfection. In summary, our study suggested that omega-3 PUFAs might protect against AD by up-regulating MAG expression.

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