Skip to main content

Advertisement

SpringerLink
Log in

Decreased Fractalkine and Increased IP-10 Expression in Aged Brain of APPswe Transgenic Mice

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Chemokines and their receptors have been strongly implicated in the inflammatory process and pathogenesis of the neurodegenerative disorders, such as Alzheimer’s disease (AD). In the present study, we examined the expression of chemokines, fractalkine, interferon-inducible protein-10 (IP-10) and macrophage inflammatory protein-1α (MIP-1α) by immunohistochemistry in the brain of transgenic mice APPSWE (Tg2576) at ages of 9, 11, and 17 months, which over-express a mutated form of human amyloid precursor protein (APP). Decreased fractalkine and increased IP-10 expression in cerebral cortex and hippocampus were found at ages of 9 and 17 months in Tg2576 mice when compared with age-matched control mice. On the contrary, MIP-1α expression showed no difference between Tg2576 mice and aged controls and was not influenced by ages. β-amyloid (Aβ) positive plaques were co-located with the intense IP-10 expression. The finding suggests fractalkine and IP-10 may participate in the pathogenesis of AD; and could be new therapeutic strategies for neuroprotection.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Akiyama H, Barger S, Barnum S et al (2000) Inflammation and Alzheimer’s disease. Neurobiol Aging 21:383–421

    Article  PubMed  CAS  Google Scholar 

  2. Johnstone M, Gearing AJ, Miller KM (1999) A central role for astrocytes in the inflammatory response to beta-amyloid; chemokines, cytokines and reactive oxygen species are produced. J Neuroimmunol 93:182–193

    Article  PubMed  CAS  Google Scholar 

  3. Xia MQ, Bacskai BJ, Knowles RB et al (2000) Expression of the chemokine receptor CXCR3 on neurons and the elevated expression of its ligand IP-10 in reactive astrocytes: in vitro ERK1/2 activation and role in Alzheimer’s disease. J Neuroimmunol 108:227–235

    Article  PubMed  CAS  Google Scholar 

  4. Smits HA, Rijsmus A, van Loon JH et al (2002) Amyloid-beta-induced chemokine production in primary human macrophages and astrocytes. J Neuroimmunol 127:160–168

    Article  PubMed  CAS  Google Scholar 

  5. Hsiao K, Chapman P, Nilsen S et al (1996) Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274:99–102

    Article  PubMed  CAS  Google Scholar 

  6. Frautschy SA, Yang F, Irrizarry M et al (1998) Microglial response to amyloid plaques in APPsw transgenic mice. Am J Pathol 152:307–317

    PubMed  CAS  Google Scholar 

  7. Irizarry MC, McNamara M, Fedorchak K et al (1997) APPSw transgenic mice develop age-related A beta deposits and neuropil abnormalities, but no neuronal loss in CA1. J Neuropathol Exp Neurol 56:965–973

    Article  PubMed  CAS  Google Scholar 

  8. Harrison JK, Jiang Y, Chen S et al (1998) Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc Natl Acad Sci USA 95:10896–108901

    Article  PubMed  CAS  Google Scholar 

  9. Re DB, Przedborski S (2006) Fractalkine: moving from chemotaxis to neuroprotection. Nat Neurosci 9:859–861

    Article  PubMed  CAS  Google Scholar 

  10. Mizuno T, Kawanokuchi J, Numata K et al (2003) Production and neuroprotective functions of fractalkine in the central nervous system. Brain Res 979:65–70

    Article  PubMed  CAS  Google Scholar 

  11. Cardona AE, Pioro EP, Sasse ME et al (2006) Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 9:917–924

    Article  PubMed  CAS  Google Scholar 

  12. Bajetto A, Bonavia R, Barbero S et al (2001) Chemokines and their receptors in the central nervous system. Front Neuroendocrinol 22:147–184

    Article  PubMed  CAS  Google Scholar 

  13. Cartier L, Hartley O, Dubois-Dauphin M et al (2005) Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases. Brain Res Brain Res Rev 48:16–42

    Article  PubMed  CAS  Google Scholar 

  14. Goldberg SH, van der Meer P, Hesselgesser J et al (2001) CXCR3 expression in human central nervous system diseases. Neuropathol Appl Neurobiol 27:127–138

    Article  PubMed  CAS  Google Scholar 

  15. Wang X, Ellison JA, Siren AL et al (1998) Prolonged expression of interferon-inducible protein-10 in ischemic cortex after permanent occlusion of the middle cerebral artery in rat. J Neurochem 71:1194–1204

    Article  PubMed  CAS  Google Scholar 

  16. Masliah E, Sisk A, Mallory M et al (1996) Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein and Alzheimer’s disease. J Neurosci 16:5795–5811

    PubMed  CAS  Google Scholar 

  17. Stalder M, Phinney A, Probst A et al (1999) Association of microglia with amyloid plaques in brains of APP23 transgenic mice. Am J Pathol 154:1673–1684

    PubMed  CAS  Google Scholar 

  18. Mandybur TI, Chuirazzi CC (1990) Astrocytes and the plaques of Alzheimer’s disease. Neurology 40:635–639

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by grants from SADF (Insamlingsstiftelsen för Alzheimer- och Demensforskning) foundation, Gun och Bertil Stohnes foundation and funds from gamla tjänarinnor foundation. The authors are very grateful to Dr. K. Hsiao (Department of Neurology, University of Minnesota, Minneapolis, USA) for providing the brains of the transgenic mouse model of Alzheimer’s disease used here.

Author information

Authors and Affiliations

  1. Division of Neurodegeneration (Novum, plan 5), Department of Neurobiology, Care Sciences and Society Karolinska Institute, Karolinska University Hospital Huddinge, 141 86, Stockholm, Sweden

    Rui-Sheng Duan, Xin Yang, Zhi-Guo Chen, Ming-Ou Lu & Jie Zhu

  2. Department of Neurology, The First Hospital, Jilin University, Changchun, China

    Xin Yang & Jie Zhu

  3. MRC Neurochemical Pathology Unit, Newcastle General Hospital, NE4 6BE, Newcastle Upon Tyne, UK

    Chris Morris

  4. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet Dainippon Sumitomo Pharma Alzheimer Center (KASPAC), Karolinska Institutet, Huddinge, Sweden

    Bengt Winblad

Authors
  1. Rui-Sheng Duan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xin Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhi-Guo Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ming-Ou Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chris Morris
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bengt Winblad
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jie Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jie Zhu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Duan, RS., Yang, X., Chen, ZG. et al. Decreased Fractalkine and Increased IP-10 Expression in Aged Brain of APPswe Transgenic Mice. Neurochem Res 33, 1085–1089 (2008). https://doi.org/10.1007/s11064-007-9554-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-007-9554-z

Keywords

Search

Navigation