Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease
| Autor: | Rico Laage, Jochen H. Weishaupt, Paul Lingor, Katrin Meuer, Bettina Göricke, Armin Schneider, Wolf-Rüdiger Schäbitz, Carola Krüger, Johannes C. M. Schlachetzki, Kerstin Peters, Bach Alfred, Jörg B. Schulz, Daniela Weber, Boris Ferger, Kazuto Kobayashi, Peter Teismann, Gunnar P.H. Dietz, Claudia Pitzer, Mathias Bähr |
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| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Parkinson's disease Substantia nigra Biology Biochemistry Neuroprotection 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Dopamine Dopaminergic Cell Internal medicine medicine 030304 developmental biology 0303 health sciences MPTP Dopaminergic Neurodegeneration medicine.disease 3. Good health Endocrinology nervous system chemistry 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Neurochemistry. 97:675-686 |
| ISSN: | 0022-3042 |
| DOI: | 10.1111/j.1471-4159.2006.03727.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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