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Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease.
J Neurochem. 2006 May; 97(3):675-86.JN

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.

Authors+Show Affiliations

Department of Neurology, University of Göttingen, Waldweg 33, 37073 Göttingen, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16573658

Citation

Meuer, Katrin, et al. "Granulocyte-colony Stimulating Factor Is Neuroprotective in a Model of Parkinson's Disease." Journal of Neurochemistry, vol. 97, no. 3, 2006, pp. 675-86.
Meuer K, Pitzer C, Teismann P, et al. Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease. J Neurochem. 2006;97(3):675-86.
Meuer, K., Pitzer, C., Teismann, P., Krüger, C., Göricke, B., Laage, R., Lingor, P., Peters, K., Schlachetzki, J. C., Kobayashi, K., Dietz, G. P., 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.
Meuer K, et al. Granulocyte-colony Stimulating Factor Is Neuroprotective in a Model of Parkinson's Disease. J Neurochem. 2006;97(3):675-86. PubMed PMID: 16573658.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease. AU - Meuer,Katrin, AU - Pitzer,Claudia, AU - Teismann,Peter, AU - Krüger,Carola, AU - Göricke,Bettina, AU - Laage,Rico, AU - Lingor,Paul, AU - Peters,Kerstin, AU - Schlachetzki,Johannes C M, AU - Kobayashi,Kazuto, AU - Dietz,Gunnar P H, AU - Weber,Daniela, AU - Ferger,Boris, AU - Schäbitz,Wolf-Rüdiger, AU - Bach,Alfred, AU - Schulz,Jörg B, AU - Bähr,Mathias, AU - Schneider,Armin, AU - Weishaupt,Jochen H, Y1 - 2006/03/29/ PY - 2006/4/1/pubmed PY - 2006/6/23/medline PY - 2006/4/1/entrez SP - 675 EP - 86 JF - Journal of neurochemistry JO - J Neurochem VL - 97 IS - 3 N2 - 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. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/16573658/Granulocyte_colony_stimulating_factor_is_neuroprotective_in_a_model_of_Parkinson's_disease_ L2 - https://doi.org/10.1111/j.1471-4159.2006.03727.x DB - PRIME DP - Unbound Medicine ER -