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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
- Authors
- Issue Date
- 2008-01-02
- Publisher
- Elsevier
- Citation
- Brain Res. 1194, 130-137
- Keywords
- 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
- Abstract
- 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.
- ISSN
- 0006-8993 (Print)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18166168
http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6SYR-4R98K8V-1-F&_cdi=4841&_user=168665&_orig=search&_coverDate=02%2F15%2F2008&_sk=988059999&view=c&wchp=dGLbVzW-zSkzk&md5=929f5c8f417e6b2956f7027b3f138b51&ie=/sdarticle.pdf
https://hdl.handle.net/10371/68449
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