Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease

Katrin Meuer, Claudia Pitzer, Peter Teismann, Carola Krüger, Bettina Göricke, Rico Laage, Paul Lingor, Kerstin Peters, Johannes C M Schlachetzki, Kazuto Kobayashi, Gunnar P H Dietz, Daniela Weber, Boris Ferger, Wolf-Rüdiger Schäbitz, Alfred Bach, Jörg B Schulz, Mathias Bähr, Armin Schneider, Jochen H Weishaupt

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91 Citations (Scopus)

Abstract

We have recently shown that the hematopoietic Granulocyte-Colony Stimulating Factor (G-CSF) is neuroprotective in rodent stroke models, and that this action appears to be mediated via a neuronal G-CSF receptor. Here, we report that the G-CSF receptor is expressed in rodent dopaminergic substantia nigra neurons, suggesting that G-CSF might be neuroprotective for dopaminergic neurons and a candidate molecule for the treatment of Parkinson's disease. Thus, we investigated protective effects of G-CSF in 1-methyl-4-phenylpyridinium (MPP+)-challenged PC12 cells and primary neuronal midbrain cultures, as well as in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. Substantial protection was found against MPP+-induced dopaminergic cell death in vitro. Moreover, subcutaneous application of G-CSF at a dose of 40 microg/Kg body weight daily over 13 days rescued dopaminergic substantia nigra neurons from MPTP-induced death in aged mice, as shown by quantification of tyrosine hydroxylase-positive substantia nigra cells. Using HPLC, a corresponding reduction in striatal dopamine depletion after MPTP application was observed in G-CSF-treated mice. Thus our data suggest that G-CSF is a novel therapeutic opportunity for the treatment of Parkinson's disease, because it is well-tolerated and already approved for the treatment of neutropenic conditions in humans.
Original languageEnglish
Pages (from-to)675-86
Number of pages12
JournalJournal of Neurochemistry
Volume97
Issue number3
DOIs
Publication statusPublished - May 2006

Keywords

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • 3,4-Dihydroxyphenylacetic Acid
  • Animals
  • Blotting, Northern
  • Brain
  • Cell Count
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Disease Models, Animal
  • Dopamine
  • Embryo, Mammalian
  • Gene Expression
  • Granulocyte Colony-Stimulating Factor
  • Green Fluorescent Proteins
  • Homovanillic Acid
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurons
  • Neuroprotective Agents
  • Parkinsonian Disorders
  • RNA, Messenger
  • Rats
  • Rats, Wistar
  • Receptors, Granulocyte Colony-Stimulating Factor
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Tyrosine 3-Monooxygenase
  • apoptosis
  • dopaminergic neurons
  • G-CSF
  • MPTP
  • neurodegeneration
  • Parkinson's disease

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  • Cite this

    Meuer, K., Pitzer, C., Teismann, P., Krüger, C., Göricke, B., Laage, R., Lingor, P., Peters, K., Schlachetzki, J. C. M., Kobayashi, K., Dietz, G. P. H., Weber, D., Ferger, B., Schäbitz, W-R., Bach, A., Schulz, J. B., Bähr, M., Schneider, A., & Weishaupt, J. H. (2006). Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease. Journal of Neurochemistry, 97(3), 675-86. https://doi.org/10.1111/j.1471-4159.2006.03727.x