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.

Enhanced glutamate, IP3 and cAMP activity in the cerebral cortex of Unilateral 6-hydroxydopamine induced Parkinson's rats: Effect of 5-HT, GABA and bone marrow cell supplementation

“…For one, immunological reactions are avoided and it also bypasses many of the ethical issues that surround the use of embryonic cells. Recent study shows that post-symptomatic treatment with granulocyte colony-stimulating factor (G-CSF) in 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) mouse model of PD rats can promote the regeneration of dopaminergic neurons in the SNpc and restore nigrostriatal function [51]. 5-HT and GABA are involved in a variety of cellular processes which includes neurogenesis, proliferation and morphology [9-15].…”

Pathogenesis-Targeted, Disease-Modifying Therapies in Parkinson Disease

“…Granulocyte colony-stimulating factor, a hematopoietic growth factor, has demonstrated neuroprotection in a PD rodent model [149]. Currently, a phase II study is evaluating the potential disease-modifying effect of recombinant granulocyte colony-stimulating factor (filgrastim) in early stage PD [150].…”

Neuroprotection by 6-(methylsulfinyl)hexyl isothiocyanate in a 6-hydroxydopamine mouse model of Parkinson׳s disease

“…Neuronal survival in the SN was expressed as the percentage of THpositive neurons on the lesioned side, with respect to the contralateral, intact side. In the absence of a stereological count, this approach was chosen to avoid methodological biases due to interindividual differences, and has been previously used to assess the extent of 6-OHDA-induced lesion in the SN (McCollum et al, 2010;Blandini et al, 2007;Armentero et al, 2006;Paul et al, 2004). The intensity of TH immunoreactivity in STR was measured using AxioVision Rel software (Zeiss) and results were expressed as percentage of TH density on the lesioned side with respect to the contralateral side.…”