G-CSF protects motoneurons against axotomy-induced apoptotic death in neonatal mice.
BACKGROUND
Granulocyte colony stimulating factor (G-CSF) is a growth factor essential for generation of neutrophilic granulocytes. Apart from this hematopoietic function, we have recently uncovered potent neuroprotective and regenerative properties of G-CSF in the central nervous system (CNS). The G-CSF receptor and G-CSF itself are expressed in alpha motoneurons, G-CSF protects motoneurons, and improves outcome in the SOD1(G93A) transgenic mouse model for amyotrophic lateral sclerosis (ALS). In vitro, G-CSF acts anti-apoptotically on motoneuronal cells. Due to the pleiotrophic effects of G-CSF and the complexity of the SOD1 transgenic ALS models it was however not possible to clearly distinguish between directly mediated anti-apoptotic and indirectly protective effects on motoneurons. Here we studied whether G-CSF is able to protect motoneurons from purely apoptotic cell death induced by a monocausal paradigm, neonatal sciatic nerve axotomy.


RESULTS
We performed sciatic nerve axotomy in neonatal mice overexpressing G-CSF in the CNS and found that G-CSF transgenic mice displayed significantly higher numbers of surviving lumbar motoneurons 4 days following axotomy than their littermate controls. Also, surviving motoneurons in G-CSF overexpressing animals were larger, suggesting additional trophic effects of this growth factor.


CONCLUSIONS
In this model of pure apoptotic cell death the protective effects of G-CSF indicate direct actions of G-CSF on motoneurons in vivo. This shows that G-CSF exerts potent anti-apoptotic activities towards motoneurons in vivo and suggests that the protection offered by G-CSF in ALS mouse models is due to its direct neuroprotective activity.
Henriques
Alexandre
A
SYGNIS Bioscience, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany.
Pitzer
Claudia
C
Dupuis
Luc
L
Schneider
Armin
A
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D001369:Axons / Q000502:physiology; D019771:Axotomy; D001921:Brain / Q000378:metabolism; D002452:Cell Count; D048429:Cell Size; D002470:Cell Survival / Q000502:physiology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D008159:Lumbar Vertebrae; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D012584:Sciatic Nerve / Q000293:injuries* / Q000503:physiopathology*; D013116:Spinal Cord / Q000503:physiopathology
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor; D002795:Choline O-Acetyltransferase