Facteurs cellulaires et moléculaires influençant la régénération axonale dans les systèmes nerveux central et périphérique
|Abstract:||The cellular and molecular responses that are activated after spinal cord and peripheral nerve injuries are quite distinct. These processes help restore tissue integrity and facilitate axonal regeneration in the injured peripheral nervous system (PNS). In the injured central nervous system (CNS), axonal regrowth is believed to be prevented by several myelin-associated inhibitors. The goal of this study is to examine and measure mRNA expression for the most studied myelin-associated inhibitors in the brain before and after a spinal cord contusion. Results show that NGR1, NGR2 and LINGO-1 are widely expressed throughout the mouse brain. In contrast, the co-receptor p75NTR is more specifically expressed in neuronal descending pathways from the brainstem, whereas TROY mRNA expression is absent. Notably, expression for these receptors was not modulated after trauma. Because myelin debris are efficiently cleared by immune cells after PNS lesion, axonal regeneration can proceed. To prove the link between axonal regeneration and the recruitment of immune cells, we have studied sciatic nerve regeneration in the CD11b-TKmt-30 transgenic mouse model in which the recruitment of myeloid cells is severely impeded by ganciclovir treatments. Results demonstrate that depletion of myeloid CD11b+ cells leads to severe deficits in recovery of sensory-motor functions that are associated with axonal regeneration failure, myelin debris accumulation, decrease of neurotrophin expression, and vascular destabilization and/or angiogenesis inhibition. Thus, CD11b+ myeloid cells are required to stimulate axonal regeneration via multiple mechanims. These results also suggest that the limited access of immune cells in the injured CNS could be, at least partly, responsible for the lack of regeneration of central axons.|
|Document Type:||Thèse de doctorat|
|Open Access Date:||13 April 2018|
|Collection:||Thèses et mémoires|
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