2. Academic Validation
  3. 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

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

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.

Figures
Products