Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

GDNF is not required for catecholaminergic neuron survival in vivo

Nature Neuroscience volume 18, pages 319–322 (2015)Cite this article

Subjects

To the Editor:

Glial cell line–derived neurotrophic factor (GDNF) has been tested in clinical trials to treat Parkinson's disease with promising, but variable, results. Improvement of therapeutic effectiveness requires solid understanding of the physiological role of GDNF in the maintenance of the adult brain catecholamine system. However, existing data on this issue is contradictory. Using three complementary approaches, we found that, independent of the time of reduction, Gdnf is not required for maintenance of catecholaminergic neurons in adult mice.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Generation of Gdnf floxed mice and catecholamine system analysis after crosses to Nestin-Cre.
Figure 2: Dopamine system analysis after striatal Gdnf reduction by AAV5-Cre injection in adult mice.
Figure 3: Dopamine system analyses after Gdnf reduction in adult mice.

References

  1. Lin, L.F., Doherty, D.H., Lile, J.D., Bektesh, S. & Collins, F. Science 260, 1130–1132 (1993).

    Article  CAS  Google Scholar 

  2. Arenas, E., Trupp, M., Akerud, P. & Ibanez, C.F. Neuron 15, 1465–1473 (1995).

    Article  CAS  Google Scholar 

  3. Meissner, W.G. et al. Nat. Rev. Drug Discov. 10, 377–393 (2011).

    Article  CAS  Google Scholar 

  4. Airaksinen, M.S. & Saarma, M. Nat. Rev. Neurosci. 3, 383–394 (2002).

    Article  CAS  Google Scholar 

  5. Jain, S. et al. J. Neurosci. 26, 11230–11238 (2006).

    Article  CAS  Google Scholar 

  6. Kramer, E.R. et al. PLoS Biol. 5, e39 (2007).

    Article  Google Scholar 

  7. Pascual, A. et al. Nat. Neurosci. 11, 755–761 (2008).

    Article  CAS  Google Scholar 

  8. Tronche, F. et al. Nat. Genet. 23, 99–103 (1999).

    Article  CAS  Google Scholar 

  9. Heuer, A., Smith, G.A., Lelos, M.J., Lane, E.L. & Dunnett, S.B. Behav. Brain Res. 228, 30–43 (2012).

    Article  CAS  Google Scholar 

  10. Grealish, S., Mattsson, B., Draxler, P. & Bjorklund, A. Eur. J. Neurosci. 31, 2266–2278 (2010).

    Article  Google Scholar 

  11. Hudson, J.L. et al. Brain Res. 626, 167–174 (1993).

    Article  CAS  Google Scholar 

  12. Liu, Y. et al. PLoS ONE 5, e13533 (2010).

    Article  CAS  Google Scholar 

  13. Taraviras, S. et al. Development 126, 2785–2797 (1999).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank S. Wiss and K. Rautio for expert technical assistance. J.-O.A. was supported by the Academy of Finland grants 136591, 140983 and 263700, the US National Institutes of Health (NS 0708259) and by the Institute of Biotechnology. M.S. was supported by grants from Sigrid Jusélius Foundation, H. Lundbeck Foundation, M. J. Fox Foundation for Parkinson's Research, Academy of Finland (grant 11186236), US National Institutes of Health (NS 0708259) and the University of Helsinki. T.P.P. was supported by Päivikki and Sakari Sohlberg Foundation. A.B. was supported by grants from the Swedish Research Council. Mouse Behavioural Phenotyping Facility. V.V. is supported by Biocenter Finland. E.C. is supported by the ERC iPlasticity project (322742), Sigrid Jusélius foundation and the Academy of Finland. S.G. was supported by a postdoctoral stipend from the Swedish Brain Foundation (Hjärnfonden). K.V. is supported by a grant from BnM. J.K. was supported by Research Foundation of the University of Helsinki and The Finnish Cultural Foundation.

Author information

Author notes

  1. Jaakko Kopra and Carolina Vilenius: These authors contributed equally to this work

  2. Mart Saarma and Jaan-Olle Andressoo: These authors jointly directed this work.

Authors and Affiliations

  1. Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland

    Jaakko Kopra & T Petteri Piepponen

  2. Institute of Biotechnology, University of Helsinki, Helsinki, Finland

    Carolina Vilenius, Mari-Anne Härma, Kärt Varendi, Mart Saarma & Jaan-Olle Andressoo

  3. Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden

    Shane Grealish & Anders Björklund

  4. Neuroscience Center, University of Helsinki, Helsinki, Finland

    Jesse Lindholm, Eero Castrén & Vootele Võikar

Authors
  1. Jaakko Kopra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carolina Vilenius
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shane Grealish
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mari-Anne Härma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kärt Varendi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jesse Lindholm
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Eero Castrén
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vootele Võikar
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Anders Björklund
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. T Petteri Piepponen
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Mart Saarma
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jaan-Olle Andressoo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

J.-O.A. designed and generated the GDNF conditional knockout mice, K.V., C.V., J.-O.A. and M.-A.H. performed qPCR measurements, J.-O.A. and M.-A.H. performed GDNF ELISA, J.K. and C.V. performed immunohistochemistry and stereology, J.K., C.V. and S.G. dissected the brains, J.K. measured dopamine levels and optical density, S.G. carried out AAV-Cre injections, C.V. did tamoxifen injections, J.L., C.V. and S.G. performed all of the behavioral assays, J.-O.A., M.S., T.P.P., A.B., V.V. and E.C. planned the experiments, M.S., J.-O.A., T.P.P. and A.B. provided funding, and J.K. and J.-O.A. prepared the figures and wrote the paper.

Corresponding author

Correspondence to Jaan-Olle Andressoo.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–3, Supplementary Table 1 and Supplementary Methods (PDF 1262 kb)

Supplementary Methods Checklist

Reporting Checklist for Nature Neuroscience (PDF 124 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kopra, J., Vilenius, C., Grealish, S. et al. GDNF is not required for catecholaminergic neuron survival in vivo. Nat Neurosci 18, 319–322 (2015). https://doi.org/10.1038/nn.3941

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn.3941

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing