Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease

Katrin Meuer, Claudia Pitzer, Peter Teismann, Carola Krüger, Bettina Göricke, Rico Laage, Paul Lingor, Kerstin Peters, Johannes C M Schlachetzki, Kazuto Kobayashi, Gunnar P H Dietz, Daniela Weber, Boris Ferger, Wolf-Rüdiger Schäbitz, Alfred Bach, Jörg B Schulz, Mathias Bähr, Armin Schneider, Jochen H Weishaupt

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)675-86
Number of pages12
JournalJournal of Neurochemistry
Volume97
Issue number3
DOIs
Publication statusPublished - May 2006

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Granulocyte Colony-Stimulating Factor
Parkinson Disease
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Substantia Nigra
Granulocyte Colony-Stimulating Factor Receptors
Neurons
Rodentia
1-Methyl-4-phenylpyridinium
Corpus Striatum
Macrophage Colony-Stimulating Factor
Dopaminergic Neurons
PC12 Cells
Tyrosine 3-Monooxygenase
Cell death
Mesencephalon
Dopamine
Cell Death
Stroke
High Pressure Liquid Chromatography
Body Weight

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

Cite this

Meuer, K., Pitzer, C., Teismann, P., Krüger, C., Göricke, B., Laage, R., ... Weishaupt, J. H. (2006). Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease. Journal of Neurochemistry, 97(3), 675-86. https://doi.org/10.1111/j.1471-4159.2006.03727.x

Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease. / 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, Wolf-Rüdiger; Bach, Alfred; Schulz, Jörg B; Bähr, Mathias; Schneider, Armin; Weishaupt, Jochen H.

In: Journal of Neurochemistry, Vol. 97, No. 3, 05.2006, p. 675-86.

Research output: Contribution to journalArticle

Meuer, K, Pitzer, C, Teismann, P, Krüger, C, Göricke, B, Laage, R, Lingor, P, Peters, K, Schlachetzki, JCM, Kobayashi, K, Dietz, GPH, Weber, D, Ferger, B, Schäbitz, W-R, Bach, A, Schulz, JB, Bähr, M, Schneider, A & Weishaupt, JH 2006, 'Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease', Journal of Neurochemistry, vol. 97, no. 3, pp. 675-86. https://doi.org/10.1111/j.1471-4159.2006.03727.x
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, Wolf-Rüdiger ; Bach, Alfred ; Schulz, Jörg B ; Bähr, Mathias ; Schneider, Armin ; Weishaupt, Jochen H. / Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease. In: Journal of Neurochemistry. 2006 ; Vol. 97, No. 3. pp. 675-86.
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AU - Laage, Rico

AU - Lingor, Paul

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AU - Kobayashi, Kazuto

AU - Dietz, Gunnar P H

AU - Weber, Daniela

AU - Ferger, Boris

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KW - Receptors, Granulocyte Colony-Stimulating Factor

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Transfection

KW - Tyrosine 3-Monooxygenase

KW - apoptosis

KW - dopaminergic neurons

KW - G-CSF

KW - MPTP

KW - neurodegeneration

KW - Parkinson's disease

U2 - 10.1111/j.1471-4159.2006.03727.x

DO - 10.1111/j.1471-4159.2006.03727.x

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