Post-MPTP treatment with granulocyte colony-stimulating factor improves nigrostriatal function in the mouse model of Parkinson's disease.

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.