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

Research output: Contribution to journalArticlepeer-review

95 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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