Granulocyte-macrophage colony-stimulating factor promotes survival of dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced murine Parkinson's disease model

Eur J Neurosci. 2009 Mar;29(5):891-900. doi: 10.1111/j.1460-9568.2009.06653.x. Epub 2009 Feb 24.


Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine that has the potential for clinical application. The biological effects of GM-CSF have been well characterized, and include stimulation of bone marrow hematopoietic stem cell proliferation and inhibition of apoptosis of hematopoietic cells. In contrast, the therapeutic effects of GM-CSF on the central nervous system in acute injury such as stroke and spinal cord injury have been reported only recently. To better understand the protective effect of GM-CSF on dopaminergic neurons in Parkinson's disease (PD), we investigated the effect of GM-CSF on the survival of dopamine neurons and changes in locomotor behavior in a murine PD model. We investigated the neuroprotective effects of GM-CSF in 1-methyl-4-phenylpyridinium (MPP+)-treated PC12 cells as well as in embryonic mouse primary mesencephalic neurons (PMNs) in vitro. To investigate the role of GM-CSF in vivo, we prepared a mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) PD model, and examined the effects of GM-CSF on dopaminergic neuron survival in the substantia nigra and on locomotor behavior. Treatment with GM-CSF significantly reduced MPP+-induced dopaminergic cell death in PC12 cells and PMNs in vitro. GM-CSF modulated the expression of apoptosis-related proteins, Bcl-2 and Bax, in vitro. Furthermore, administration of GM-CSF (50 microg/kg body weight/day) in vivo for 7 days protected dopaminergic neurons in the substantia nigra and improved locomotor behavior in a mouse MPTP model of PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine*
  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chromatography, High Pressure Liquid / methods
  • Corpus Striatum / cytology
  • Corpus Striatum / drug effects
  • Disease Models, Animal
  • Dopamine / metabolism*
  • Embryo, Mammalian
  • Exploratory Behavior / drug effects
  • Gene Expression Regulation / drug effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Locomotion / drug effects
  • Membrane Potentials / drug effects
  • Mice
  • Neurons / drug effects*
  • Parkinson Disease, Secondary / chemically induced*
  • Parkinson Disease, Secondary / physiopathology
  • Parkinson Disease, Secondary / prevention & control*
  • Patch-Clamp Techniques / methods
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Receptor, Macrophage Colony-Stimulating Factor / metabolism
  • Substantia Nigra / pathology
  • Time Factors
  • Tyrosine 3-Monooxygenase / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism


  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Tyrosine 3-Monooxygenase
  • Receptor, Macrophage Colony-Stimulating Factor
  • Dopamine