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

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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https://www.hal.inserm.fr/inserm-00663774
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Submitted on : Friday, January 27, 2012 - 2:28:00 PM
Last modification on : Friday, October 23, 2020 - 4:33:26 PM
Long-term archiving on: : Monday, November 19, 2012 - 3:10:57 PM

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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, BioMed Central, 2010, 11 (1), pp.25. ⟨10.1186/1471-2202-11-25⟩. ⟨inserm-00663774⟩

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