• 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, and Jochen H Weishaupt.
• Department of Neurology, University of Göttingen, Waldweg 33, 37073 Göttingen, Germany.
• J. Neurochem. 2006 May 1;97(3):675-86.

AbstractWe 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.

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