title: Ciliary neurotrophic factor controls progenitor migration during remyelination in the adult rodent brain.
abstract: Ciliary neurotrophic factor (CNTF) has been shown to be expressed after brain lesions and in particular after demyelination. Here, we addressed the role of this cytokine in the regulation of neural progenitor migration in the adult rodent brain. Using an acute model of demyelination, we show that CNTF is strongly re-expressed after lesion and is involved in the postlesional mobilization of endogenous progenitors that participate in the myelin regenerative process. We show that CNTF controls the migration of subventricular zone (SVZ)-derived neural progenitors toward the demyelinated corpus callosum. Furthermore, an ectopic source of CNTF in adult healthy brains changes SVZ-derived neural progenitors' migratory behavior that migrate toward the source by activation of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway. Using various in vitro assays (Boyden chambers, explants, and video time-lapse imaging), we demonstrate that CNTF controls the directed migration of SVZ-derived progenitors and oligodendrocyte precursors. Altogether, these results demonstrate that in addition to its neuroprotective activity and its role in progenitor survival and maturation, CNTF acts as a chemoattractant and participates in the recruitment of endogenous progenitors during myelin repair.
authors: Aix-Marseille Université, Institut de Biologie du Développement de Marseille de Luminy, Unité Mixte de Recherche 7288, 13288 Marseille, France.
authors: Julien
authors: J
authors: Vernerey
authors: Magali
authors: M
authors: Macchi
authors: Karine
authors: K
authors: Magalon
authors: Myriam
authors: M
authors: Cayre
authors: Pascale
authors: P
authors: Durbec
mesh_terms: D000818:Animals; D000963:Antimetabolites; D001921:Brain / Q000166:cytology / Q000502:physiology*; D001973:Bromodeoxyuridine; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology; D020934:Ciliary Neurotrophic Factor / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology; D014162:Transfection
chemical_list: D000963:Antimetabolites; D002630:Chemotactic Factors; D020934:Ciliary Neurotrophic Factor; D001973:Bromodeoxyuridine