Detailed Information

Granulocyte-colony stimulating factor attenuates striatal degeneration with activating survival pathways in 3-nitropropionic acid model of Huntington's disease

Cited 26 time in Web of Science Cited 28 time in Scopus

Lee, Soon-Tae; Park, Jung-Eun; Kim, Dong-Hyun; Kim, Seungchan; Im, Woo-Seok; Kang, Lami; Jung, Se Hee; Kim, Min-Wook; Chu, Kon; Kim, Manho

Issue Date
Brain Res. 1194, 130-137
AnimalsCorpus Striatum/drug effects/*pathologyDisease Models, AnimalDrug InteractionsGene Expression Regulation/drug effects/physiologyGranulocyte Colony-Stimulating Factor/*therapeutic useHuntington Disease/*chemically induced/*complicationsIn Situ Nick-End LabelingMaleOrganic Chemicals/diagnostic useRatsRats, Inbred LewSignal Transduction/*drug effects/physiologyStatistics, NonparametricNeurodegenerative Diseases/drug therapy/etiology/pathologyNitro CompoundsPropionic 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)
Files in This Item:
There are no files associated with this item.
Appears in Collections:


Item View & Download Count

  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.