Skip to main content

Advertisement

SpringerLink
Log in

Effects of acidic oligosaccharide sugar chain on amyloid oligomer-induced impairment of synaptic plasticity in rats

  • Research Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Soluble amyloid-β protein (Aβ) oligomers have been recognized to be early and key intermediates in Alzheimer’s disease-related synaptic dysfunction. In this study, using in vitro electrophysiology, we investigated interactions of the acidic oligosaccharide sugar chain (AOSC), a marine-derived acidic oligosaccharide, with oligomeric Aβ. We found that the inhibition of long-term potentiation (LTP) induced by Aβ oligomers can be dose dependently reversed by the application of AOSC, whereas AOSC alone did not alter normal LTP induction. Interestingly, treatment with Aβ monomers with or without AOSC did not affect LTP induction. Additionally, when fresh-made Aβ was co-incubated with AOSC before in vitro testing, there was no impairment of LTP induction. The results from Western blots demonstrated that AOSC prevent the aggregation of Aβ oligomers. These findings indicate that AOSC may reverse Aβ oligomer-mediated cytotoxicity by directly disrupting the amyloid oligomer aggregation, and this action is concentration dependent. Thus, we propose that AOSC might be a potential therapeutic drug for Alzheimer’s disease due to its protection against oligomeric Aβ-induced dysfunction of synaptic plasticity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Ahmed M et al (2010) Structural conversion of neurotoxic amyloid-beta(1–42) oligomers to fibrils. Nat Struct Mol Biol 17:561–567

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Barry AE, Klyubin I, Mc Donald JM, Mably AJ, Farrell MA, Scott M, Walsh DM, Rowan MJ (2011) Alzheimer’s disease brain-derived amyloid-β-mediated inhibition of LTP in vivo is prevented by immunotargeting cellular prion protein. J Neurosci 31:7259–7263

    Article  CAS  PubMed  Google Scholar 

  • Conlberg JA, Li J, Uversky VN, Fink AL (2002) Heparin and other glycosaminoglycans stimulate the formation of amyloid fibrils from a-synulcein in vitro. Biogeosciences 41:1502–1511

    Google Scholar 

  • Demattos RB, Lu J, Tang Y, Racke MM, Delong CA, Tzaferis JA, Hole JT, Forster BM, McDonnell PC, Liu F, Kinley RD, Jordan WH, Hutton ML (2012) A plaque-specific antibody clears existing β-amyloid plaques in Alzheimer’s disease mice. Neuron 76:908–920

    Article  CAS  PubMed  Google Scholar 

  • De-Paula VJ, Radanovic M, Diniz BS, Forlenza OV (2012) Alzheimer’s disease. Subcell Biochem 65:329–352

    Article  CAS  PubMed  Google Scholar 

  • Dinamarca MC, Colombres M, Cerpa W, Bonansco C, Inestrosa NC (2008) Beta-amyloid oligomers affect the structure and function of the postsynaptic region: role of the Wnt signaling pathway. Neurodegener Dis 5:149–152

    Article  CAS  PubMed  Google Scholar 

  • Fan Y, Hu J, Li J, Yang Z, Xin X, Wang J, Ding J, Geng M (2005) Effect of acidic oligosaccharide sugar chain on scopolamine-induced memory impairment in rats and its related mechanisms. Neurosci Lett 374:222–226

    Article  CAS  PubMed  Google Scholar 

  • Giuffrida ML, Caraci F, Pignataro B, Cataldo S, De Bona P, Bruno V, Molinaro G, Pappalardo G, Messina A, Palmigiano A, Garozzo D, Nicoletti F, Rizzarelli E, Copani A (2009) Beta-amyloid monomers are neuroprotective. J Neurosci 29:10582–10587

    Article  CAS  PubMed  Google Scholar 

  • Guo X, Xin X, Gan L, Nie Q, Geng M (2006) Determination of the accessibility of acidic oligosaccharide sugar chain to blood–brain barrier using surface plasmon resonance. Biol Pharm Bull 29:60–63

    Article  CAS  PubMed  Google Scholar 

  • Hoyer W, Grönwall C, Jonsson A, Ståhl S, Härd T (2008) Stabilization of a beta-hairpin in monomeric Alzheimer’s amyloid-beta peptide inhibits amyloid formation. Proc Natl Acad Sci 105:5099–5104

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hu J, Geng M, Li J, Xin X, Wang J, Tang M, Zhang J, Zhang X, Ding J (2004) Acidic oligosaccharide sugar chain, a marine-derived acidic oligosaccharide, inhibits the cytotoxicity and aggregation of amyloid beta protein. J Pharmacol Sci 95:248–255

    CAS  PubMed  Google Scholar 

  • Jan A, Hartley DM, Lashuel HA (2010) Preparation and characterization of toxic Abeta aggregates for structural and functional studies in Alzheimer’s disease research. Nat Protoc 5:1186–1209

    Article  CAS  PubMed  Google Scholar 

  • Kayed R, Head E, Sarsoza F, Saing T, Cotman CW, Necula M, Margol L, Wu J, Breydo L, Thompson JL, Rasool S, Gurlo T, Butler P, Glabe CG (2007) Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers. Mol Neurodegener 2:18

    Article  PubMed Central  PubMed  Google Scholar 

  • Klyubin I, Walsh DM, Lemere CA, Cullen WK, Shankar GM, Betts V, Spooner ET, Jiang L, Anwyl R, Selkoe DJ, Rowan MJ (2005) Amyloid beta protein immunotherapy neutralizes Abeta oligomers that disrupt synaptic plasticity in vivo. Nat Med 11:556–561

    Article  CAS  PubMed  Google Scholar 

  • Klyubin I, Cullen WK, Hu NW, Rowan MJ (2012) Alzheimer’s disease Aβ assemblies mediating rapid disruption of synaptic plasticity and memory. Mol Brain 17:5–25

    Google Scholar 

  • Lauren J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM (2009) Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nat 457:1128–1132

    Google Scholar 

  • LeVine H III (2004) Alzheimer’s β-peptide oligomer formation at physiologic concentrations. Anal Biochem 335:81–90

    Article  CAS  PubMed  Google Scholar 

  • Schenk DB, Seubert P, Grundman M, Black R (2005) A beta immunotherapy: lessons learned for potential treatment of Alzheimer’s disease. Neurodegener Dis 2:255–260

    Article  CAS  PubMed  Google Scholar 

  • Schmidt SD, Mazzella MJ, Nixon RA, Mathews PM (2012) Aβ measurement by enzyme-linked immunosorbent assay. Methods Mol Biol 849:507–527

    Article  CAS  PubMed  Google Scholar 

  • Selkoe DJ (2008) Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior. Behav Brain Res 192:106–113

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Shankar GM, Li S, Mehta TH, Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA, Regan CM, Walsh DM, Sabatini BL, Selkoe DJ (2008) Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med 14:837–842

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Singh S, Kushwah AS, Singh R, Farswan M, Kaur R (2012) Current therapeutic strategy in Alzheimer’s disease. Eur Rev Med Pharmacol Sci 16:1651–1664

    CAS  PubMed  Google Scholar 

  • Tai LM, Bilousova T, Jungbauer L, Roeske SK, Youmans KL, Yu C, Poon WW, Cornwell LB, Miller CA, Vinters HV, Van Eldik LJ, Fardo DW, Estus S, Bu G, Gylys KH, Ladu MJ (2013) Levels of soluble apolipoprotein E/Amyloid-β (Aβ) complex are reduced and oligomeric Aβ increased with APOE4 and Alzheimer disease in a transgenic mouse model and human samples. J Biol Chem 288:5914–5926

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Takahashi RH, Milner TA, Li F, Nam EE, Edgar MA, Yamaguchi H, Beal MF, Xu H, Greengard P, Gouras GK (2002) Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology. Am J Pathol 161:1869–1879

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tam JH, Pasternak SH (2012) Amyloid and Alzheimer’s disease: inside and out. Can J Neurol Sci 39:286–298

    PubMed  Google Scholar 

  • Walsh DM, Selkoe DJ (2007) A beta oligomers—a decade of discovery. J Neurochem 101:1172–1184

    Article  CAS  PubMed  Google Scholar 

  • Walsh DM, Klyubuin I, Fadeeva J, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, Selkoe DJ (2002) Naturally secreted oligomers of the Alzheimer amyloid β-protein potently inhibit long-term potentiation in vivo. Nature 416:535–539

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Walsh DM, Rowan MJ, Selkoe DJ, Anwyl R (2004) Block of long-term potentiation by naturally secreted and synthetic amyloid beta-peptide in hippocampal slices is mediated via activation of the kinases c-Jun N-terminal kinase, cyclin-dependent kinase 5, and p38 mitogen-activated protein kinase as well as metabotropic glutamate receptor type 5. J Neurosci 24:3370–3378

    Article  CAS  PubMed  Google Scholar 

  • Wang S, Li J, Xia W, Geng M (2007a) A marine-derived acidic oligosaccharide sugar chain specifically inhibits neuronal cell injury mediated by beta-amyloid-induced astrocyte activation in vitro. Neurol Res 29:96–102

    Article  PubMed  Google Scholar 

  • Wang XJ, Chen XH, Yang XY, Geng MY, Wang LM (2007b) Acidic oligosaccharide sugar chain, a marine-derived oligosaccharide, activates human glial cell line-derived neurotrophic factor signaling. Neurosci Lett 417:176–180

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge helpful discussions critical reading of the manuscript with Dr. Istvan Mody. This work was supported by grants from the National Nature Science Foundation of China (81271209, 81070873), Ningbo Key Science and Technology Project (2011C51006), Disciplinary Project of Ningbo University (SZXl1075), Medicine Foundation of Zhejiang (2008A145) and the K.C. Wong Magna Fund in Ningbo University.

Author information

Authors and Affiliations

  1. Zhejiang Provincial Key Laboratory of Pathophysiology, Medical School, Ningbo University, Ningbo, 315211, China

    Lan Chang, Fushun Li, Xiaowei Chen, Shujun Xu, Chuang Wang & Qinwen Wang

  2. Medical School, Shanghai Jiaotong University, Shanghai, 200240, China

    Hongzhuan Chen

Authors
  1. Lan Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fushun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaowei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shujun Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chuang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hongzhuan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Qinwen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Lan Chang or Qinwen Wang.

Additional information

Lan Chang and Fushun Li contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chang, L., Li, F., Chen, X. et al. Effects of acidic oligosaccharide sugar chain on amyloid oligomer-induced impairment of synaptic plasticity in rats. Metab Brain Dis 29, 683–690 (2014). https://doi.org/10.1007/s11011-014-9521-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-014-9521-8

Keywords

Search

Navigation