title: Programming Hippocampal Neural Stem/Progenitor Cells into Oligodendrocytes Enhances Remyelination in the Adult Brain after Injury.
abstract: Demyelinating diseases are characterized by a loss of oligodendrocytes leading to axonal degeneration and impaired brain function. Current strategies used for the treatment of demyelinating disease such as multiple sclerosis largely rely on modulation of the immune system. Only limited treatment options are available for treating the later stages of the disease, and these treatments require regenerative therapies to ameliorate the consequences of oligodendrocyte loss and axonal impairment. Directed differentiation of adult hippocampal neural stem/progenitor cells (NSPCs) into oligodendrocytes may represent an endogenous source of glial cells for cell-replacement strategies aiming to treat demyelinating disease. Here, we show that Ascl1-mediated conversion of hippocampal NSPCs into mature oligodendrocytes enhances remyelination in a diphtheria-toxin (DT)-inducible, genetic model for demyelination. These findings highlight the potential of targeting hippocampal NSPCs for the treatment of demyelinated lesions in the adult brain.
authors.affiliation: Brain Research Institute, Faculty of Medicine and Science, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich and ETH, 8057 Zurich, Switzerland.
authors.forename: Simon M G
authors.initials: SM
authors.lastname: Braun
authors.affiliation: Brain Research Institute, Faculty of Medicine and Science, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich and ETH, 8057 Zurich, Switzerland.
authors.forename: Gregor-Alexander
authors.initials: GA
authors.lastname: Pilz
authors.affiliation: Brain Research Institute, Faculty of Medicine and Science, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Raquel A C
authors.initials: RA
authors.lastname: Machado
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Moss
authors.affiliation: Neuroscience Center Zurich, University of Zurich and ETH, 8057 Zurich, Switzerland; Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Becher
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Toni
authors.affiliation: Brain Research Institute, Faculty of Medicine and Science, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich and ETH, 8057 Zurich, Switzerland. Electronic address: jessberger@hifo.uzh.ch.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jessberger
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001930:Brain Injuries / Q000473:pathology*; D003711:Demyelinating Diseases / Q000209:etiology / Q000473:pathology*; D004167:Diphtheria Toxin / Q000633:toxicity; D006624:Hippocampus / Q000166:cytology* / Q000254:growth & development / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004167:Diphtheria Toxin; C499317:Ascl1 protein, mouse