Granulocyte-colony stimulating factor (G-CSF) enhances recovery in mouse model of Parkinson's disease.
BACKGROUND
Granulocyte-colony stimulating factor (G-CSF) is used routinely in clinical practice for the treatment of neutropenia and to increase generation of hematopoietic stem cells in bone marrow donors. A growing body of literature on the neurotrophic effects of G-CSF has led to clinical trials in stroke, Alzheimer's disease (AD) and Parkinson's disease (PD).


OBJECTIVE
The primary objective of this study was to determine if G-CSF administration would rescue the nigro-striatal system and restore locomotor function after completion of a sub-acute course of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration (30mg/kg i.p. for 5 days) in 12 month-old mice. A secondary aim was to determine if G-CSF affects the neuro-inflammatory response by modulating microglial activation in striatum and midbrain.


RESULTS
MPTP-treated mice were impaired on the rotometer test after the last dose of the toxicant and remained impaired until euthanasia. MPTP-treated mice that were given an 8-day regimen of G-CSF starting 2 days after the last dose of toxicant enhanced motor performance compared to the MPTP alone group. MPTP treatment depleted striatal DA (DA) levels; G-CSF given after MPTP resulted in a partial, significant repletion of DA levels. Total microglial burden in the striatum was increased significantly in MPTP-treated mice and was reduced after G-CSF rescue.


CONCLUSIONS
G-CSF enhances recovery of DA nigro-striatal function from MPTP toxicity in part by modulating the microglial response to injury. The G-CSF receptor may provide a novel target for modifying the disease process in Parkinson's disease.
James Haley Veterans Affairs Medical Center, Tampa, FL, USA.
Shijie
S
Song
Vasyl
V
Sava
Amanda
A
Rowe
Kunyu
K
Li
Chuanhai
C
Cao
Takashi
T
Mori
Juan
J
Sanchez-Ramos
D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D011897:Random Allocation; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology
D016179:Granulocyte Colony-Stimulating Factor; D004298:Dopamine