G-CSF protects motoneurons against axotomy-induced apoptotic death in neonatal mice

BMC Neuroscience

Research Article

Armin Schneider¹  Claudia Pitzer¹  Alexandre Henriques²  Luc Dupuis³ 

[1] SYGNIS Bioscience, Im Neuenheimer Feld 515, 69120, Heidelberg, Germany;SYGNIS Bioscience, Im Neuenheimer Feld 515, 69120, Heidelberg, Germany;University of Strasbourg, Faculty of Medicine, UMRS692, Strasbourg, France;INSERM U692, Strasbourg, France;University of Strasbourg, Faculty of Medicine, UMRS692, Strasbourg, France;INSERM U692, Strasbourg, France;

关键词: Amyotrophic Lateral Sclerosis;    Sciatic Nerve;    Granulocyte Colony Stimulate Factor;    Motoneuron Survival;    Ventral Horn;   

DOI  :  10.1186/1471-2202-11-25

 received in 2009-06-25, accepted in 2010-02-23,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundGranulocyte 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 α 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.ResultsWe 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.ConclusionsIn 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.

【 授权许可】

Unknown   
© Henriques et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.