The effect of the hypoxia-inducible GM-CSF expression system using water-soluble lipopolymer (WSLP) in neuroal cell injuries in vitro.

초록

Objective: Granulocyte macrophage–colony stimulating factor (GM-CSF) is a hematopoietic cytokine which can be approved for clinical application. However, its therapeutic effects in the central nervous system have only been revealed recently. We investigated whether the GM-CSF can protect dopaminergic neuron in Parkinson’s disease (PD) model. Materials & Methods: PC12 cells and embryonic mouse primary mesencephalic neurons (PMNs) culture with or without GM-CSF pre-treatment were treated with 1-methyl-4-phenylpyridinium (MPP+) in culture. We also prepared a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD animal model, and GM-CSF was administrated daily for consecutive 7 days. Quantification of tyrosine hydroxylase (TH)-positive cells was performed to evaluate the damage of substantia nigra. And we carried out the open field test in animal models. Results: GM-CSF showed protective effect on doparminergic neurons both in vitro and in vivo. GM-CSF significantly reduced MPP+ induced dopaminergic cell death in PC12 cells and PMNs in vitro. The administration of GM-CSF protected dopaminergic neurons from cell death in mouse PD model. Furthermore, GM-CSF improved locomotor behavior and rescued dopamine level in mouse PD model. Conclusion: GM-CSF shows Neuroprotective effect in our experimental PD model, but the underlying mechanisms remains largely unresolved. GM-CSF has been proved safe for hamatologic patients, while considering GM-CSF as a clinical therapeutic agent for PD patients. We also need to study more for resolving safety in treatment of neural diseases such as Parkinson’s disease.