G-CSF protects motoneurons against axotomy-induced apoptotic death in neonatal mice. - Archive ouverte HAL Access content directly
Journal Articles BMC Neuroscience Year : 2010

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

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Abstract

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.
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inserm-00663774 , version 1 (27-01-2012)

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Alexandre Henriques, Claudia Pitzer, Luc Dupuis, Armin Schneider. G-CSF protects motoneurons against axotomy-induced apoptotic death in neonatal mice.. BMC Neuroscience, 2010, 11 (1), pp.25. ⟨10.1186/1471-2202-11-25⟩. ⟨inserm-00663774⟩

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