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Granulocyte‐colony stimulating factor is neuroprotective in a model of Parkinson's disease
Author(s) -
Meuer Katrin,
Pitzer Claudia,
Teismann Peter,
Krüger Carola,
Göricke Bettina,
Laage Rico,
Lingor Paul,
Peters Kerstin,
Schlachetzki Johannes C. M.,
Kobayashi Kazuto,
Dietz Gunnar P. H.,
Weber Daniela,
Ferger Boris,
Schäbitz WolfRüdiger,
Bach Alfred,
Schulz Jörg B.,
Bähr Mathias,
Schneider Armin,
Weishaupt Jochen H.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03727.x
Subject(s) - substantia nigra , mptp , dopaminergic , neuroprotection , tyrosine hydroxylase , dopamine , parkinson's disease , pharmacology , hematopoietic growth factor , medicine , endocrinology , granulocyte colony stimulating factor , biology , neuroscience , microbiology and biotechnology , haematopoiesis , disease , chemotherapy , stem cell
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 μg/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.