Molecular Neurobiology

, Volume 53, Issue 5, pp 3146–3153 | Cite as

Endogenous Docosahexaenoic Acid (DHA) Prevents Aβ1–42 Oligomer-Induced Neuronal Injury

  • Yuan Tan
  • Huixia Ren
  • Zhe Shi
  • Xiaoli Yao
  • Chengwei He
  • Jing-X Kang
  • Jian-Bo Wan
  • Peng Li
  • Ti-Fei Yuan
  • Huanxing Su
Article

Abstract

The intake of the polyunsaturated fatty acid docosahexaenoic acid (DHA) or n-3 fatty acid has been associated with reduced risk of Alzheimer’s disease (AD) in epidemiological reports. However, the underlying mechanism remains to be elucidated. Here, we report that exogenous DHA administration could protect neurons against Aβ oligomer-induced injury both in vitro and in vivo, partly through reducing the endoplasmic reticulum (ER) stress, and preventing cell apoptosis. In transgenic fat-1 mice with enriched ω-3 fatty acids, Aβ oligomers induced fewer neuronal losses, when compared to wild-type (WT) mice. We conclude that endogenous DHA are neuroprotective in pathogenesis processes of AD.

Keywords

Alzheimer’s disease Aβ oligomers DHA Omega-3 Fat-1 mice 

References

  1. 1.
    Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol 8(2):101–112CrossRefPubMedGoogle Scholar
  2. 2.
    Krafft GA, Klein WL (2010) ADDLs and the signaling web that leads to Alzheimer’s disease. Neuropharmacology 59(4-5):230–242CrossRefPubMedGoogle Scholar
  3. 3.
    Kuo YM, Emmerling MR, Vigo-Pelfrey C, Kasunic TC, Kirkpatrick JB, Murdoch GH et al (1996) Water-soluble Abeta (N-40, N-42) oligomers in normal and Alzheimer disease brains. J Biol Chem 271(8):4077–4081CrossRefPubMedGoogle Scholar
  4. 4.
    Roher AE, Chaney MO, Kuo YM, Webster SD, Stine WB, Haverkamp LJ et al (1996) Morphology and toxicity of Abeta-(1-42) dimer derived from neuritic and vascular amyloid deposits of Alzheimer’s disease. J Biol Chem 271(34):20631–20635CrossRefPubMedGoogle Scholar
  5. 5.
    Walsh DM, Tseng BP, Rydel RE, Podlisny MB, Selkoe DJ (2000) The oligomerization of amyloid beta-protein begins intracellularly in cells derived from human brain. Biochemistry 39(35):10831–10839CrossRefPubMedGoogle Scholar
  6. 6.
    Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS et al (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416(6880):535–539CrossRefPubMedGoogle Scholar
  7. 7.
    Gong Y, Chang L, Viola KL, Lacor PN, Lambert MP, Finch CE et al (2003) Alzheimer’s disease-affected brain: presence of oligomeric a beta ligands (ADDLs) suggests a molecular basis for reversible memory loss. Proc Natl Acad Sci U S A 100(18):10417–10422CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Lesne S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A et al (2006) A specific amyloid-beta protein assembly in the brain impairs memory. Nature 440(7082):352–357CrossRefPubMedGoogle Scholar
  9. 9.
    Kalmijn S, Feskens EJ, Launer LJ, Kromhout D (1997) Polyunsaturated fatty acids, antioxidants, and cognitive function in very old men. Am J Epidemiol 145(1):33–41CrossRefPubMedGoogle Scholar
  10. 10.
    Kalmijn S, Launer LJ, Ott A, Witteman JC, Hofman A, Breteler MM (1997) Dietary fat intake and the risk of incident dementia in the Rotterdam study. Ann Neurol 42(5):776–782CrossRefPubMedGoogle Scholar
  11. 11.
    Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Wilson RS et al (2003) Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol 60(7):940–946CrossRefPubMedGoogle Scholar
  12. 12.
    Barberger-Gateau P, Letenneur L, Deschamps V, Peres K, Dartigues JF, Renaud S (2002) Fish, meat, and risk of dementia: cohort study. BMJ 325(7370):932–933CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Lim WS, Gammack JK, Van Niekerk J, Dangour AD (2006) Omega 3 fatty acid for the prevention of dementia. Cochrane Database Syst Rev. 2006 (1):Cd005379Google Scholar
  14. 14.
    Fotuhi M, Mohassel P, Yaffe K (2009) Fish consumption, long-chain omega-3 fatty acids and risk of cognitive decline or Alzheimer disease: a complex association. Nat Clin Pract Neurol 5(3):140–152CrossRefPubMedGoogle Scholar
  15. 15.
    Kang ZB, Ge Y, Chen Z, Cluette-Brown J, Laposata M, Leaf A et al (2001) Adenoviral gene transfer of Caenorhabditis elegans n--3 fatty acid desaturase optimizes fatty acid composition in mammalian cells. Proc Natl Acad Sci U S A 98(7):4050–4054CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Kang JX, Wang J, Wu L, Kang ZB (2004) Transgenic mice: fat-1 mice convert n-6 to n-3 fatty acids. Nature 427(6974):504CrossRefPubMedGoogle Scholar
  17. 17.
    Fa M, Orozco IJ, Francis YI, Saeed F, Gong Y, Arancio O (2010) Preparation of oligomeric beta-amyloid 1-42 and induction of synaptic plasticity impairment on hippocampal slices. J Vis Exp 14:(41). doi:10.3791/1884
  18. 18.
    Klein WL (2002) ADDLs & protofibrils—the missing links? Neurobiol Aging 23(2):231–235CrossRefPubMedGoogle Scholar
  19. 19.
    Hsia AY, Masliah E, McConlogue L, Yu GQ, Tatsuno G, Hu K et al (1999) Plaque-independent disruption of neural circuits in Alzheimer’s disease mouse models. Proc Natl Acad Sci U S A 96(6):3228–3233CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Nilsberth C, Westlind-Danielsson A, Eckman CB, Condron MM, Axelman K, Forsell C et al (2001) The ‘Arctic’ APP mutation (E693G) causes Alzheimer’s disease by enhanced Abeta protofibril formation. Nat Neurosci 4(9):887–893CrossRefPubMedGoogle Scholar
  21. 21.
    Prasad MR, Lovell MA, Yatin M, Dhillon H, Markesbery WR (1998) Regional membrane phospholipid alterations in Alzheimer’s disease. Neurochem Res 23(1):81–88CrossRefPubMedGoogle Scholar
  22. 22.
    Soderberg M, Edlund C, Kristensson K, Dallner G (1991) Fatty acid composition of brain phospholipids in aging and in Alzheimer’s disease. Lipids 26(6):421–425CrossRefPubMedGoogle Scholar
  23. 23.
    Song JH, Miyazawa T (2001) Enhanced level of n-3 fatty acid in membrane phospholipids induces lipid peroxidation in rats fed dietary docosahexaenoic acid oil. Atherosclerosis 155(1):9–18CrossRefPubMedGoogle Scholar
  24. 24.
    Johnson EJ, McDonald K, Caldarella SM, Chung HY, Troen AM, Snodderly DM (2008) Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women. Nutr Neurosci 11(2):75–83CrossRefPubMedGoogle Scholar
  25. 25.
    Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving G, Garlind A et al (2006) Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol 63(10):1402–1408CrossRefPubMedGoogle Scholar
  26. 26.
    Kotani S, Sakaguchi E, Warashina S, Matsukawa N, Ishikura Y, Kiso Y et al (2006) Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction. Neurosci Res 56(2):159–164CrossRefPubMedGoogle Scholar
  27. 27.
    Chiu CC, Su KP, Cheng TC, Liu HC, Chang CJ, Dewey ME et al (2008) The effects of omega-3 fatty acids monotherapy in Alzheimer’s disease and mild cognitive impairment: a preliminary randomized double-blind placebo-controlled study. Prog Neuropsychopharmacol Biol Psychiatry 32(6):1538–1544CrossRefPubMedGoogle Scholar
  28. 28.
    van de Rest O, Geleijnse JM, Kok FJ, van Staveren WA, Dullemeijer C, Olderikkert MG et al (2008) Effect of fish oil on cognitive performance in older subjects: a randomized, controlled trial. Neurology 71(6):430–438CrossRefPubMedGoogle Scholar
  29. 29.
    Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C et al (2010) Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA 304(17):1903–1911CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Yuan Tan
    • 1
  • Huixia Ren
    • 1
  • Zhe Shi
    • 1
  • Xiaoli Yao
    • 2
  • Chengwei He
    • 1
  • Jing-X Kang
    • 3
  • Jian-Bo Wan
    • 1
  • Peng Li
    • 1
  • Ti-Fei Yuan
    • 4
  • Huanxing Su
    • 1
  1. 1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical SciencesUniversity of MacauMacaoChina
  2. 2.Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated HospitalSun Yat-Sen UniversityGuangzhouChina
  3. 3.Laboratory for Lipid Medicine and Technology, The Department of MedicineMassachusetts General Hospital and Harvard Medical SchoolBostonUSA
  4. 4.School of PsychologyNanjing Normal UniversityNanjingChina

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