title: Hes3 expression in the adult mouse brain is regulated during demyelination and remyelination.
abstract: Hes3 is a component of the STAT3-Ser/Hes3 Signaling Axis controlling the growth and survival of neural stem cells and other plastic cells. Pharmacological activation of this pathway promotes neuronal rescue and behavioral recovery in models of ischemic stroke and Parkinson's disease. Here we provide initial observations implicating Hes3 in the cuprizone model of demyelination and remyelination. We focus on the subpial motor cortex of mice because we detected high Hes3 expression. This area is of interest as it is impacted both in human demyelinating diseases and in the cuprizone model. We report that Hes3 expression is reduced at peak demyelination and is partially restored within 1 week after cuprizone withdrawal. This raises the possibility of Hes3 involvement in demyelination/remyelination that may warrant additional research. Supporting a possible role of Hes3 in the maintenance of oligodendrocyte markers, a Hes3 null mouse strain shows lower levels of myelin basic protein in undamaged adult mice, compared to wild-type controls. We also present a novel method for culturing the established oligodendrocyte progenitor cell line oli-neu in a manner that maintains Hes3 expression as well as its self-renewal and differentiation potential, offering an experimental tool to study Hes3. Based upon this approach, we identify a Janus kinase inhibitor and dbcAMP as powerful inducers of Hes3 gene expression. We provide a new biomarker and cell culture method that may be of interest in demyelination/remyelination research.
authors.affiliation: Technische Universität Dresden, Department of Internal Medicine III, Dresden 01307, Germany.
authors.forename: Louiza
authors.initials: L
authors.lastname: Toutouna
authors.affiliation: Technische Universität Dresden, Department of Internal Medicine III, Dresden 01307, Germany.
authors.forename: Polyxeni
authors.initials: P
authors.lastname: Nikolakopoulou
authors.affiliation: Technische Universität Dresden, Department of Internal Medicine III, Dresden 01307, Germany.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Poser
authors.affiliation: Technische Universität Dresden, Department of Internal Medicine III, Dresden 01307, Germany.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Masjkur
authors.affiliation: Technische Universität Dresden, Department of Internal Medicine III, Dresden 01307, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Arps-Forker
authors.affiliation: Technische Universität Dresden, Department of Clinical Pathobiochemistry, Dresden 01307, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Troullinaki
authors.affiliation: Technische Universität Dresden, Department of Clinical Pathobiochemistry, Dresden 01307, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Grossklaus
authors.affiliation: Technische Universität Dresden, Department of Internal Medicine III, Dresden 01307, Germany; Center for Regenerative Therapies Dresden, 01307 Dresden, Germany.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Bosak
authors.affiliation: Technische Universität Dresden, Department of Internal Medicine III, Dresden 01307, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Friedrich
authors.affiliation: Zentrum für klinische Neurowissenschaften, Klinik und Poliklinik für Neurologie, Universitätsklinikum Carl Gustav Carus Dresden, Technische Universität Dresden, Germany.
authors.forename: Tjalf
authors.initials: T
authors.lastname: Ziemssen
authors.affiliation: Technische Universität Dresden, Department of Internal Medicine III, Dresden 01307, Germany.
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
authors.affiliation: Technische Universität Dresden, Department of Clinical Pathobiochemistry, Dresden 01307, Germany.
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
authors.affiliation: Technische Universität Dresden, Department of Internal Medicine III, Dresden 01307, Germany; Center for Regenerative Therapies Dresden, 01307 Dresden, Germany; Department of Stem Cell Biology, Centre for Biomolecular Sciences, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK. Electronic address: Andreas.Theotokis@uniklinikum-dresden.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Androutsellis-Theotokis
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D018929:Cell Culture Techniques; D017077:Culture Media, Conditioned; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009044:Motor Cortex / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017077:Culture Media, Conditioned; D003471:Cuprizone; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C411886:Hes3 protein, mouse
keywords: Brain; Hes3; Myelin; Oligodendrocyte precursor; Regeneration