S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Neurology (신경과학교실) Journal Papers (저널논문_신경과학교실)
Granulocyte-colony stimulating factor attenuates striatal degeneration with activating survival pathways in 3-nitropropionic acid model of Huntington's disease
- Issue Date
- Brain Res. 1194, 130-137
- Animals ; Corpus Striatum/drug effects/*pathology ; Disease Models, Animal ; Drug Interactions ; Gene Expression Regulation/drug effects/physiology ; Granulocyte Colony-Stimulating Factor/*therapeutic use ; Huntington Disease/*chemically induced/*complications ; In Situ Nick-End Labeling ; Male ; Organic Chemicals/diagnostic use ; Rats ; Rats, Inbred Lew ; Signal Transduction/*drug effects/physiology ; Statistics, Nonparametric ; Neurodegenerative Diseases/drug therapy/etiology/pathology ; Nitro Compounds ; Propionic Acids
- Huntington's disease (HD) has a mitochondrial dysfunction causing the vulnerability to the excitotoxicity and activations of multiple cell death pathways. Recent evidences suggest that the hematopoietic cytokine, granulocyte-colony stimulating factor (G-CSF), exerts pleiotropic neuroprotection in acute neural injury with activating various survival pathways. Thus, we investigated whether G-CSF can modulate neurodegeneration in an HD animal model induced by 3-nitropropionic acid (3NP), which inhibits mitochondrial succinate dehydrogenase complex II. Either G-CSF (50 microg/kg/day) or saline (as vehicle) was administered intraperitoneally for 5 days with 3NP (63 mg/kg/day) continuous osmotic pump infusion into male Lewis rats. We measured motor scales (0-8) daily and sacrificed rats at 5 days. We observed that G-CSF receptors were expressed in 3NP-induced degenerating striatum. Rats treated with G-CSF showed less degree of neurologic deficits. In the G-CSF-treated rats, the striatal lesion volume measured by Nissl staining, TUNEL+ apoptotic cells, Fluorojade C+ degenerating neurons, and c-Jun+ cells were all decreased. In western blotting, G-CSF activated survival pathways including p-ERK, p-eNOS, p-STAT3, and p-Akt. In summary, G-CSF was found to have neuroprotective effects and save striatal cells through activations of survival pathways in the 3NP-induced striatal degeneration model for HD.
- 0006-8993 (Print)
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