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> Stages de M2 > Liste des stages proposés pour l’année 2016-2017 > Hedgehog and androgen signaling pathways in myelin regeneration

Hedgehog and androgen signaling pathways in myelin regeneration

proposé par Elisabeth TRAIFFORT, Petites molécules de Neuroprotection, Neurorégénération et Remyélinisation – U11 ; Le Kremlin-Bicêtre 94276

Projet de stage : Our team has recently demonstrated that Hedgehog and androgen signaling pathways, well-known for their respective role notably in brain and reproductive tract development, also promote myelin repair in various animal models of demyelination (Ferent et al, J Neurosci, 2013 ; Hussain et al, Brain, 2013). Both pathways are positive regulators of local oligodendrocyte progenitors, the major source of cells solicited to trigger the remyelination process. However the role of these pathways on the other cell types recruited towards the lesion has been much less investigated. These other cell types include i) the reactive astro- and micro-glial cells which participate in the inflammatory process and are endowed with both beneficial and deleterious effects during the repair ; ii) the progenitors generated in one of the main niche for neural stem cells in the adult brain, the subventricular zone (SVZ). The project is aimed at investigating the consequences of the genetic modulation of Hedgehog or androgen signaling pathways in the oligodendroglial lineage, reactive glial cells or SVZ progenitors during myelin repair in order to determine the role of these pathways in the recruitment, differentiation / maturation of neural progenitors and in the polarization of microglial cells. The project should increase our understanding of the mechanisms which lead to the microenvironment required for improving the endogenous capacity of the brain to self-repair in a field where small molecules able to promote myelin repair are not yet available for patients.

Techniques mises en œuvre par le stagiaire : The technical approaches include the use of transgenic mouse strains based on the Cre-lox system, primary cell cultures, immunological labelling and microscopic analyses using epifluorescence, confocal or electronic microscopy.

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