title: Inflammatory demyelination induces ependymal modifications concomitant to activation of adult (SVZ) stem cell proliferation.
abstract: Ependymal cells (E1/E2) and ciliated B1cells confer a unique pinwheel architecture to the ventricular surface of the subventricular zone (SVZ), and their cilia act as sensors to ventricular changes during development and aging. While several studies showed that forebrain demyelination reactivates the SVZ triggering proliferation, ectopic migration, and oligodendrogenesis for myelin repair, the potential role of ciliated cells in this process was not investigated. Using conventional and lateral wall whole mount preparation immunohistochemistry in addition to electron microscopy in a forebrain-targeted model of experimental autoimmune encephalomyelitis (tEAE), we show an early decrease in numbers of pinwheels, B1 cells, and E2 cells. These changes were transient and simultaneous to tEAE-induced SVZ stem cell proliferation. The early drop in B1/E2 cell numbers was followed by B1/E2 cell recovery. While E1 cell division and ependymal ribbon disruption were never observed, E1 cells showed important morphological modifications reflected by their enlargement, extended cytoskeleton, and reinforced cell-cell junction complexes overtime, possibly reflecting protective mechanisms against ventricular insults. Finally, tEAE disrupted motile cilia planar cell polarity and cilia orientation in ependymal cells. Therefore, significant ventricular modifications in ciliated cells occur early in response to tEAE suggesting a role for these cells in SVZ stem cell signalling not only during development/aging but also during inflammatory demyelination. These observations may have major implications for understanding pathophysiology of and designing therapeutic approaches for inflammatory demyelinating diseases such as MS.
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, UM-75, ICM-GH Pitié-Salpêtrière, Paris, F-75013, France.|INSERM, U1127, Paris, F-75013, France.|CNRS, UMR 7225, Paris, F-75013, France.|Cellular and Molecular Biology Research Center, Physiology Department, Babol University of Medical Sciences, Babol, Iran.
authors.forename: Fereshteh
authors.identifier: 0000-0001-9285-1571
authors.initials: F
authors.lastname: Pourabdolhossein
authors.affiliation: Multiple Sclerosis and Neural Regeneration Research Unit Instituto de Investigación and H.U.P. La Fe Avda. Fernando Abril Martorell, Valencia, 106 46026, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Gil-Perotín
authors.affiliation: Laboratory of Comparative Neurobiology, Department of Cell Biology, Instituto Cavanilles de Biodiversidad y Biologia Evolutiva, University of Valencia, CIBERNED, Paterna, Valencia, 46980, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Garcia-Belda
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, UM-75, ICM-GH Pitié-Salpêtrière, Paris, F-75013, France.|INSERM, U1127, Paris, F-75013, France.|CNRS, UMR 7225, Paris, F-75013, France.
authors.forename: Aurelien
authors.initials: A
authors.lastname: Dauphin
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, UM-75, ICM-GH Pitié-Salpêtrière, Paris, F-75013, France.|INSERM, U1127, Paris, F-75013, France.|CNRS, UMR 7225, Paris, F-75013, France.
authors.forename: Sabah
authors.initials: S
authors.lastname: Mozafari
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, UM-75, ICM-GH Pitié-Salpêtrière, Paris, F-75013, France.|INSERM, U1127, Paris, F-75013, France.|CNRS, UMR 7225, Paris, F-75013, France.|Achucarro Basque Center for Neuroscience and Departamento de Neurociencias, Facultad de Medicina, Universidad del Pais Vasco Barrio la Sarriena s/n 48940 Leioa, Spain.
authors.forename: Vanja
authors.initials: V
authors.lastname: Tepavcevic
authors.affiliation: Laboratory of Comparative Neurobiology, Department of Cell Biology, Instituto Cavanilles de Biodiversidad y Biologia Evolutiva, University of Valencia, CIBERNED, Paterna, Valencia, 46980, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Manuel Garcia Verdugo
authors.affiliation: Sorbonne Universités UPMC Univ Paris 06, UM-75, ICM-GH Pitié-Salpêtrière, Paris, F-75013, France.|INSERM, U1127, Paris, F-75013, France.|CNRS, UMR 7225, Paris, F-75013, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Baron-Van Evercooren
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology*; D000818:Animals; D049109:Cell Proliferation / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology*; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000378:metabolism; D020547:Lateral Ventricles / Q000166:cytology*; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis; D009457:Neuroglia / Q000166:cytology
keywords: B1 cells; ependymal cells; inflammatory demyelination; subventricular zone; tEAE