Hes3 expression in the adult mouse brain is regulated during demyelination and remyelination

Toutouna, Louiza and Nikolakopoulou, Polyxeni and Poser, Steven W. and Masjkur, Jimmy and Arps-Forker, Carina and Troullinaki, Maria and Grossklaus, Sylvia and Bosak, Viktoria and Friedrich, Ulrike and Ziemssen, Tjalf and Bornstein, Stefan R. and Chavakis, Triantafyllos and Androutsellis-Theotokis, Andreas (2016) Hes3 expression in the adult mouse brain is regulated during demyelination and remyelination. Brain Research, 1642 . pp. 124-130. ISSN 1872-6240

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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.

Item Type: Article
Keywords: Hes3; Myelin; Oligodendrocyte precursor; Brain; Regeneration
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Cancer and Stem Cells
Identification Number: 10.1016/j.brainres.2016.03.014
Depositing User: Eprints, Support
Date Deposited: 12 May 2017 13:53
Last Modified: 13 May 2017 16:40
URI: http://eprints.nottingham.ac.uk/id/eprint/42833

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