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Interferon-γ induces progressive nigrostriatal degeneration and basal ganglia calcification

Nature Neuroscience volume 14, pages 694–696 (2011)Cite this article

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Abstract

We found that CNS-directed expression of interferon-γ (IFN-γ) resulted in basal ganglia calcification, reminiscent of human idiopathic basal ganglia calcification (IBGC), and nigrostriatal degeneration. Our results indicate that IFN-γ mediates age-progressive nigrostriatal degeneration in the absence of exogenous stressors. Further study of this model may provide insight into selective nigrostriatal degeneration in human IBGC and other Parkinson syndromes.

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Figure 1: rAAV2/1-mediated mIFN-γ expression leads to extensive gliosis and selective basal ganglia calcification in the brains of wild-type mice.
Figure 2: Selective and age-progressive nigrostriatal degeneration in wild-type mice expressing rAAV2/1–mIFN-γ.

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References

  1. Schroder, K., Hertzog, P.J., Ravasi, T. & Hume, D.A. J. Leukoc. Biol. 75, 163–189 (2004).

    Article  CAS  Google Scholar 

  2. Chakrabarty, P. et al. FASEB J. 24, 548–559 (2010).

    Article  CAS  Google Scholar 

  3. Chakrabarty, P. et al. J. Immunol. 184, 5333–5343 (2010).

    Article  CAS  Google Scholar 

  4. Baba, Y., Broderick, D.F., Uitti, R.J., Hutton, M.L. & Wszolek, Z.K. Mayo Clin. Proc. 80, 641–651 (2005).

    Article  CAS  Google Scholar 

  5. Corbin, J.G. et al. Mol. Cell. Neurosci. 7, 354–370 (1996).

    Article  CAS  Google Scholar 

  6. Horwitz, M.S., Evans, C.F., McGavern, D.B., Rodriguez, M. & Oldstone, M.B. Nat. Med. 3, 1037–1041 (1997).

    Article  CAS  Google Scholar 

  7. Manyam, B.V., Walters, A.S. & Narla, K.R. Mov. Disord. 16, 258–264 (2001).

    Article  CAS  Google Scholar 

  8. Paschali, A. et al. Clin. Nucl. Med. 34, 421–423 (2009).

    Article  Google Scholar 

  9. Savoldi, F., Nappi, G., Martignoni, E. & Bono, G. Acta Neurol. (Napoli) 2, 231–239 (1980).

    CAS  Google Scholar 

  10. Devos, D., Defebvre, L. & Bordet, R. Fundam. Clin. Pharmacol. 24, 407–421 (2010).

    Article  CAS  Google Scholar 

  11. Jang, H., Boltz, D.A., Webster, R.G. & Smeyne, R.J. Biochim. Biophys. Acta 1792, 714–721 (2009).

    Article  CAS  Google Scholar 

  12. Shelton, G.D. et al. Muscle Nerve 22, 156–165 (1999).

    Article  CAS  Google Scholar 

  13. Morishima, T., Morita, M., Kato, T., Hoshino, Y. & Kimura, H. Eur. J. Neurol. 9, 521–525 (2002).

    Article  CAS  Google Scholar 

  14. Mount, M.P. et al. J. Neurosci. 27, 3328–3337 (2007).

    Article  CAS  Google Scholar 

  15. Frank-Cannon, T.C., Alto, L.T., McAlpine, F.E. & Tansey, M.G. Mol. Neurodegener. 4, 47 (2009).

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the US National Institutes of Health/National Institute on Aging (T.E.G.), the Ellison Medical Foundation (T.E.G.) and American Health Assistance Foundation (P.D.).

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Authors and Affiliations

  1. Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA

    Paramita Chakrabarty, Carolina Ceballos-Diaz, Amanda Beccard, Christopher Janus & Todd E Golde

  2. Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA

    Wen-Lang Lin, Karen Jansen-West, Dennis Dickson & Pritam Das

  3. Department of Neurology, University of Florida, Gainesville, Florida, USA

    Nikolaus R McFarland

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  1. Paramita Chakrabarty
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  2. Carolina Ceballos-Diaz
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  4. Amanda Beccard
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  5. Karen Jansen-West
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  6. Nikolaus R McFarland
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  7. Christopher Janus
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  9. Pritam Das
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  10. Todd E Golde
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Contributions

P.C. conducted the experiments and wrote the manuscript. C.C.-D. prepared the rAAV2/1 virus and performed quantitative real-time RT-PCR. W.-L.L. performed the electron micrography. A.B. and K.J.-W. provided technical assistance. C.J. conducted the behavioral analysis. N.R.M. and P.D. assisted with study design and interpretation. D.D. provided human tissue and conducted neuropathological analysis and interpretation. T.E.G. coordinated the research, supervised the project and assisted in manuscript preparation.

Corresponding author

Correspondence to Todd E Golde.

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The authors declare no competing financial interests.

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Chakrabarty, P., Ceballos-Diaz, C., Lin, WL. et al. Interferon-γ induces progressive nigrostriatal degeneration and basal ganglia calcification. Nat Neurosci 14, 694–696 (2011). https://doi.org/10.1038/nn.2829

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