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 language | English |
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Pages (from-to) | 675-86 |
Number of pages | 12 |
Journal | Journal of Neurochemistry |
Volume | 97 |
Issue number | 3 |
DOIs | |
Publication status | Published - 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