Skip to main content

Advertisement

SpringerLink
Log in

PrP106-126 and Aβ1-42 Peptides Induce BV-2 Microglia Chemotaxis and Proliferation

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Transmissible spongiform encephalopathies (TSEs) and Alzheimer's disease (AD) belong to a growing family of neurodegenerative disorders that is characterized by the generation of toxic protein aggregates in affected brains (PrPSc and Aβ in TSEs and AD, respectively). To better understand how protein aggregates can modulate microglial processes in these diseases, we treated BV-2 microglia with PrP106-126 or Aβ1-42 peptides individually at three different concentrations (25–100 μM PrP106-12 and 2.5–10 μM Aβ1-42) or with a mixture of PrP106-126 and Aβ1-42 peptides at specified concentrations for 6–24 h. BV-2 microglia chemotaxis, proliferation, and monocyte chemoattractant protein-1 and transforming growth factor-β1 (TGF-β1) secretion were measured and compared between treatments. The results demonstrate that PrP106-126 and Aβ1-42 peptides induce increases in all four parameters from 6 to 12 h. However, the measured indices plateaued beyond 12 h in BV-2 cells treated >50 μM PrP or >5 μM Aβ1-42, with the exception of TGF-β1 secretion, which continued to increase gradually. Overall, the results of this study indicate that these two peptides may mutually inhibit microglial chemotaxis and proliferation simultaneously via changes induced at the protein level.

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
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Arispe N, Doh M (2002) Plasma membrane cholesterol controls the cytotoxicity of Alzheimer's disease Aβ(1–40) and (1–42) peptides. Faseb J 16:1526–1536

    Article  CAS  PubMed  Google Scholar 

  • Bamberger ME, Harris ME, McDonald DR, Jens H, Landreth GE (2003) A Cell surface receptor complex for fibrillar-amyloid mediates microglial activation. The Journal of Neuroscience 23:2665–2674

    CAS  PubMed  Google Scholar 

  • Barnham KJ, Cappai R, Beyreuther K, Masters CL, Hill AF (2006) Delineating common molecular mechanisms in Alzheimer's and prion diseases. Trends Biochem Sci 31:465–472

    Article  CAS  PubMed  Google Scholar 

  • Bart D, Croes EA, Rademakers R, Broeck MVD, Cruts M et al (2003) PRNP Val 129 homozygosity increases risk for early-onset Alzheimer's disease. Ann Neurol 3:409–412

    Google Scholar 

  • Brown DR, Schmidt B, Kretzschmar HA (1996) Role of microglia and host prion protein in neurotoxicity of a prion protein fragment. NaturE 380:345–347

    Article  CAS  PubMed  Google Scholar 

  • Burdick D, Soreghan B, Kwon M, Kosmoski J, Knauer M, Henschen A et al (1992) Assembly and aggregation properties of synthetic Alzheimer's A4/beta amyloid peptide analogs. J Biol Chem 267:546–554

    CAS  PubMed  Google Scholar 

  • Checler F, Vincent B (2002) Alzheimer's and prion diseases: distinct pathologies, common proteolytic denominators. Trends Neurosci 25:616–620

    Article  CAS  PubMed  Google Scholar 

  • Chromy BA, Nowak RJ, Lambert MP (2003) Self-assembly of Aβ1-42 into globular neurotoxins. Biochemistry 42:12749–12760

    Article  CAS  PubMed  Google Scholar 

  • Ciesielski-Treska J, Grant NJ, Ulrich G, Corrotte M, Bailly Y, Haeberle AM et al (2004) Fibrillar prion peptide (106–126) and scrapie prion protein hamper phagocytosis in microglia. Glia 46:101–115

    Article  PubMed  Google Scholar 

  • Cunningham C, Boche D, Perry VH (2002) Transforming growth factor β1, the dominant cytokine in murine prion disease: influence on inflammatory cytokine synthesis and alteration of vascular extracellular matrix. Neuropathol Appl Neurobiol 28:107–119

    Article  CAS  PubMed  Google Scholar 

  • Dunzendorfer S, Kaser A, Meierhofer C, Tilg H, Wiedermann CJ (2000) Dendritic cell migration in different micropore filter assays. Immunol Lett 71:5–11

    Article  CAS  PubMed  Google Scholar 

  • Felton LM, Cunningham C, Rankine EL, Waters S, Boche D, Perry VH (2005) MCP-1 and murine prion disease: separation of early behavioural dysfunction from overt clinical disease. Neurobiol Dis 20:283–295

    Article  CAS  PubMed  Google Scholar 

  • Ferrer I, Blanco R, Carmona M, Puig B, Ribera R, Rey MJ et al (2001) Prion protein expression in senile plaques in Alzheimer's disease. Acta Neuropathol 101:49–56

    CAS  PubMed  Google Scholar 

  • Forloni G, Angeretti N, Chiesa R, Monzani E, Salmona M, Bugiani O et al (1993) Neurotoxicity of a prion protein fragment. Nature 362:543–546

    Article  CAS  PubMed  Google Scholar 

  • France M, Eiden M, Balkema-Buschmann A, Greenlee J, Schatzl H, Fast C et al (2012) Detection of PrPSc in peripheral tissues of clinically affected cattle after oral challenge with bovine spongiform encephalopathy. J Gen Virol 93:2740–2748

    Article  Google Scholar 

  • Gavín R, Ureña J, Rangel A, Pastrana MA, Requena JR, Soriano E et al (2008) Fibrillar prion peptide PrP(106–126) treatment induces Dab1 phosphorylation and impairs APP processing and Aβ production in cortical neurons. Neurobiol Dis 30:243–254

    Article  PubMed  Google Scholar 

  • Ghoshal A, Das S, Ghosh S, Mishra MK, Sharma V, Koli P et al (2007) Proinflammatory mediators released by activated microglia induces neuronal death in Japanese encephalitis. Glia 55:483–496

    Article  PubMed  Google Scholar 

  • Hainfellner JA, Wanschitz J, Kurt J, Liberski PP, Gullotta F, Budka H (1998) Coexistence of Alzheimer-type neuropathology in Creutzfeldt–Jakob disease. Acta Neuropathol 96:116–122

    Article  CAS  PubMed  Google Scholar 

  • Heneka MT (2006) Inflammation in Alzheimer's disease. Clin Neurosci Res 6:247–260

    Article  CAS  Google Scholar 

  • Horvath RJ, Nutile-McMenemy N, Alkaitis MS, Deleo JA (2008) Differential migration, LPS-induced cytokine, chemokine, and NO expression in immortalized BV-2 and HAPI cell lines and primary microglial cultures. J Neurochem 107:557–569

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ishizuka K, Kitamura T, Igata-yi R, Katsuragi S, Takamatsu J, Miyakawa T (1997) Identification of monocyte chemoattractant protein-1 in senile plaques and reactive microglia of Alzheimer's disease. Psychiatry Clin Neurosci 51:135–138

    Article  CAS  PubMed  Google Scholar 

  • Johnstone M, Gearing AJH, Miller KM (1993) A central role for astrocytes in the inflammatory response to β-amyloid; chemokines, cytokines and reactive oxygen species are produced. J Neuroimmunol 93:182–193

    Article  Google Scholar 

  • Kallithraka S, Bakker J, Clifford MN, Vallis L (2001) Correlations between saliva protein composition and some T-I parameters of astringency. Food Qual Prefer 12:145–152

    Article  Google Scholar 

  • Kaneider NC, Kaser A, Dunzendorfer S, Tilg H, Wiedermann CJ (2003) Sphingosine kinase-dependent migration of immature dendritic cells in response to neurotoxic prion protein fragment. J Virol 77:5535–5539

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Khoury JE, Toft M, Hickman SE, Means TK, Terada K, Geula C et al (2007) Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med 13:432–438

    Article  PubMed  Google Scholar 

  • Konturek PC, Bazela K, Kukharskyy V, Bauer M, Hahn EG, Schuppan D (2005) Helicobacter pylori upregulates prion protein expression in gastric mucosa: a possible link to prion disease. World J Gastroenterol 11:7651–7656

    CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  PubMed  Google Scholar 

  • Le Y, Yazawa H, Gong W, Yu Z, Ferrans VJ, Ferrans et al (2001) The neurotoxic prion peptide fragment PrP(106–126) is a chemotactic agonist for the G protein-coupled receptor formyl peptide receptor-like 1. J Immunol 166:1448–1451

    CAS  PubMed  Google Scholar 

  • Marella M, Chabry J (2004) Neurons and astrocytes respond to prion infection by inducing microglia recruitment. J Neurosci 24:620–627

    Article  CAS  PubMed  Google Scholar 

  • McGeer PL, Itagaki S, Tago H, McGeer EG (1987) Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR. Neurosci Lett 79:195–200

    Article  CAS  PubMed  Google Scholar 

  • Moustapha C, Lennart M (2009) Alzheimer's disease: a prion protein connection. Nature 457:1090–1091

    Article  Google Scholar 

  • Muhleisen H, Gehrmann J, Meyermann R (1995) Reactive microglia in Creutzfeldt–Jakob disease. Neuropathol Appl Neurobiol 6:505–517

    Article  Google Scholar 

  • Perlmutter LS, Barron E, Chui HC (1990) Morphologic association between microglia and senile plaque amyloid in Alzheimer's disease. Neurosci Lett 119:32–36

    Article  CAS  PubMed  Google Scholar 

  • Pike CJ, Walencewicz AJ, Glabe CG, Cotman CW (1991) In vitro aging of β-amyloid protein causes peptide aggregation and neurotoxicity. Brain Res 563:311–314

    Article  CAS  PubMed  Google Scholar 

  • Powers JM, Liu Y, Hair LS, Kascsack RJ, Lewis LD, Wester DD et al (1991) Concomitant Creutzfeldt–Jakob and Alzheimer diseases. Acta Neuropathol 83:95–98

    Article  CAS  PubMed  Google Scholar 

  • Prat E, Baron P, Meda L, Scarpini E, Galimberti D, Ardolino G et al (2000) The human astrocytoma cell line U373MG produces monocyte chemotactic protein (MCP)-1 upon stimulation with β-amyloid protein. Neurosci Lett 283:177–180

    Article  CAS  PubMed  Google Scholar 

  • Riemenschneider M, Klopp N, Xiang W, Wagenpfeil S, Vollmert C, Muller U et al (2004) Prion protein codon 129 polymorphism and risk of Alzheimer disease. Neurology 63:364–366

    Article  CAS  PubMed  Google Scholar 

  • Roher AE, Ball MJ, Bhave SV, Wakade AR (1991) β-Amyloid from Alzheimer disease brains inhibits sprouting and survival of sympathetic neurons. Biochem Biophys Res Commun 174:572–579

    Article  CAS  PubMed  Google Scholar 

  • Rota E, Bellone G, Rocca P, Bergamasco B, Emanuelli G, Ferrero P (2006) Increased intrathecal TGF-beta1, but not IL-12, IFN-gamma and IL-10 levels in Alzheimer's disease patients. Neurol Sci 27:33–39

    Article  CAS  PubMed  Google Scholar 

  • Safar J, Roller PP, Gajdusek DC, Gibbs CJ Jr (1993) Conformational transitions, dissociation, and unfolding of scrapie amyloid (prion) protein. J Biol Chem 268:20276–20284

    CAS  PubMed  Google Scholar 

  • Sasaki A, Yamaguchi H, Ogawa A, Sugihara S, Nakazato Y (1997) Microglia activation in early stages of amyloid beta protein deposition. Acta Neuropathol 94:316–322

    Article  CAS  PubMed  Google Scholar 

  • Small DH, McLean CA (1999) Alzheimer's disease and the amyloid β protein: what is the role of amyloid-β. Neurochem 73:443–449

    Article  CAS  Google Scholar 

  • Stine WB, Karie J, Dahlgren N, Krafft GA, LaDu MJ (2003) In vitro characterization of conditions for amyloid-beta peptide oligomerization and fibrillogenesis. J Biol Chem 278:11612–11622

    Article  CAS  PubMed  Google Scholar 

  • Tsuchiya K, Yagishita S, Ikeda K, Sano M, Taki K, Hashimoto K et al (2004) Coexistence of CJD and Alzheimer's disease: an autopsy case showing typical clinical features of CJD. Neuropathology 24:46–55

    Article  PubMed  Google Scholar 

  • Vascellari S, Orrù CD, Hughson AG, Declan K, Rona B, Wilham JM et al (2012) Prion seeding activities of mouse scrapie strains with divergent PrPSc protease sensitivities and amyloid plaque content using RT-QuIC and eQuIC. PLoS ONE 7(11):e48969

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Veerhuis BR, Familian RS (2005) Amyloid associated proteins in Alzheimer's and prion disease. Curr Drug Targets-CNS Neurol Disord 4:235–248

    Article  CAS  PubMed  Google Scholar 

  • Verma A, Prasad KN, Singh AK, Nyati KK, Gupta RK, Paliwal VK (2010) Evaluation of the MTT lymphocyte proliferation assay for the diagnosis of neurocysticercosis. J Microbiol Methods 81:175–178

    Article  CAS  PubMed  Google Scholar 

  • Voigtländer T, Klöppel S, Birner P, Jarius C, Flicker H et al (2001) Marked increase of neuronal prion protein immunoreactivity in Alzheimer's disease and human prion diseases. Acta Neuropathol 101:417–423

    PubMed  Google Scholar 

  • Vrotsos EG, Kolattukudy PE, Sugaya K (2009) MCP-1 involvement in glial differentiation of neuroprogenitor cells through APP signaling. Brain Res Bull 79:97–103

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Ministry of Agriculture, Key Program, China (Project No. 2009ZX08008-010B), the Ministry of Agriculture Key Program, China (Project No.2009ZX08007-008B), the Natural Science Foundation of China (Project No.30771622), the Natural Science Foundation of China (Project No. 31001048), and the Ph.D. Programs Foundation of the Ministry of Education of China (Project No. 20100008120002).

Author information

Authors and Affiliations

  1. National Animal TSE Lab, College of Veterinary Medicine, China Agricultural University, Beijing, China

    Jian Tu, LiFeng Yang, XiangMei Zhou, KeZong Qi, JinGuo Wang, Mohammed Kouadir, LiHua Xu, XiaoMin Yin & DeMing Zhao

  2. College of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, Anhui Province, China

    Jian Tu & KeZong Qi

  3. Key Lab of Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, China Agricultural University, Beijing, China

    Jian Tu, LiFeng Yang, XiangMei Zhou, JinGuo Wang, Mohammed Kouadir, LiHua Xu, XiaoMin Yin & DeMing Zhao

Authors
  1. Jian Tu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. LiFeng Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. XiangMei Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. KeZong Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. JinGuo Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mohammed Kouadir
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. LiHua Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. XiaoMin Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. DeMing Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to DeMing Zhao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tu, J., Yang, L., Zhou, X. et al. PrP106-126 and Aβ1-42 Peptides Induce BV-2 Microglia Chemotaxis and Proliferation. J Mol Neurosci 52, 107–116 (2014). https://doi.org/10.1007/s12031-013-0140-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-013-0140-3

Keywords

Search

Navigation