Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease.
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.
Meuer
Katrin
K
Department of Neurology, University of Göttingen, Waldweg 33, 37073 Göttingen, Germany.
Pitzer
Claudia
C
Teismann
Peter
P
Krüger
Carola
C
Göricke
Bettina
B
Laage
Rico
R
Lingor
Paul
P
Peters
Kerstin
K
Schlachetzki
Johannes C M
JC
Kobayashi
Kazuto
K
Dietz
Gunnar P H
GP
Weber
Daniela
D
Ferger
Boris
B
Schäbitz
Wolf-Rüdiger
WR
Bach
Alfred
A
Schulz
Jörg B
JB
Bähr
Mathias
M
Schneider
Armin
A
Weishaupt
Jochen H
JH
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004622:Embryo, Mammalian; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D049452:Green Fluorescent Proteins; D006719:Homovanillic Acid / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000517:prevention & control*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014162:Transfection / Q000379:methods; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018696:Neuroprotective Agents; D012333:RNA, Messenger; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D015102:3,4-Dihydroxyphenylacetic Acid; D016179:Granulocyte Colony-Stimulating Factor; D049452:Green Fluorescent Proteins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid