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Post-MPTP Treatment with Granulocyte Colony-Stimulating Factor Improves Nigrostriatal Function in the Mouse Model of Parkinson’s Disease

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Abstract

The neuroprotective effects of granulocyte colony-stimulating factor (G-CSF) were reported in several neurological disease models, including Parkinson’s disease (PD). In the present study, we investigated the therapeutic effect of G-CSF after the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD was established. G-CSF was subcutaneously administered into C57BL/6 mice that had undergone systemic MPTP injections. We found that G-CSF treatment markedly increased the number of dopaminergic neurons in the substantia nigra pars compacta (SNpc) of the G-CSF-treated group. Consistent with this finding, we found a significant increase in dopamine release under high K+ stimulation in the striatum of the G-CSF-treated animals compared to the MPTP-exposed mice. Finally, we observed a persistent recovery of locomotor function in the G-CSF-treated animals. These results suggest the potential therapeutic value of G-CSF in treating PD. However, our bromodeoxyuridine labeling experiment failed to identify any newly generated dopaminergic neurons in SNpc. This might indicate an indirect effect of G-CSF on cell proliferation. The underlying mechanism of G-CSF is under further investigation.

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Abbreviations

BrdU:

Bromodeoxyuridine

DCX:

Doublecortin

G-CSF:

Granulocyte colony-stimulating factor

G-CSFR:

G-CSF receptor

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

NSC:

Neural stem cell

PCNA:

Proliferating cell nuclear antigen

PD:

Parkinson’s disease

PFA:

Paraformaldehyde

SGZ:

Subgranular zone

SNpc:

Substantia nigra pars compacta

SVZ:

Subventricular zone

TH:

Tyrosine hydroxylase

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Acknowledgements

This study was partially supported by Charles E. Schmidt Family Foundation.

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Authors and Affiliations

  1. Department of Basic Science, Charles E. Schmidt College of Biomedical Science, Florida Atlantic University, Boca Raton, FL, 33431, USA

    Mark McCollum, Zhiyuan Ma, Eric Cohen, Rebecca Leon, Rui Tao, Jang-Yen Wu & Jianning Wei

  2. South Florida Bone Marrow Transplant/Stem Cell Institute, Boynton Beach, FL, 33437, USA

    Dipnarine Maharaj

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  1. Mark McCollum
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  2. Zhiyuan Ma
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  3. Eric Cohen
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  4. Rebecca Leon
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Correspondence to Jang-Yen Wu, Dipnarine Maharaj or Jianning Wei.

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McCollum, M., Ma, Z., Cohen, E. et al. Post-MPTP Treatment with Granulocyte Colony-Stimulating Factor Improves Nigrostriatal Function in the Mouse Model of Parkinson’s Disease. Mol Neurobiol 41, 410–419 (2010). https://doi.org/10.1007/s12035-010-8118-4

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  • DOI: https://doi.org/10.1007/s12035-010-8118-4

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