Endogenous Sox8 is a critical factor for timely remyelination and oligodendroglial cell repletion in the cuprizone model

Freudenstein D, Lippert M, Popp JS, Aprato J, Wegner M, Sock E, Haase S, Linker RA, González Alvarado MN (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 13

Article Number: 22272

Journal Issue: 1

DOI: 10.1038/s41598-023-49476-5

Abstract

Genome-wide association studies identified a single nucleotide polymorphism (SNP) downstream of the transcription factor Sox8, associated with an increased risk of multiple sclerosis (MS). Sox8 is known to influence oligodendrocyte terminal differentiation and is involved in myelin maintenance by mature oligodendrocytes. The possible link of a Sox8 related SNP and MS risk, along with the role of Sox8 in oligodendrocyte physiology prompted us to investigate its relevance during de- and remyelination using the cuprizone model. Sox8−/− mice and wildtype littermates received a cuprizone diet for 5 weeks (wk). Sox8−/− mice showed reduced motor performance and weight compared to wildtype controls. Brains were histologically analysed at the maximum of demyelination (wk 5) and on two time points during remyelination (wk 5.5 and wk 6) for oligodendroglial, astroglial, microglial and myelin markers. We identified reduced proliferation of oligodendrocyte precursor cells at wk 5 as well as reduced numbers of mature oligodendrocytes in Sox8−/− mice at wk 6. Moreover, analysis of myelin markers revealed a delay in remyelination in the Sox8−/− group, demonstrating the potential importance of Sox8 in remyelination processes. Our findings present, for the first time, compelling evidence of a significant role of Sox8 in the context of a disease model.

Authors with CRIS profile

Jessica Aprato Lehrstuhl für Biochemie und Pathobiochemie Michael Wegner Lehrstuhl für Biochemie und Pathobiochemie Elisabeth Sock Lehrstuhl für Biochemie und Pathobiochemie

Involved external institutions

Universitätsklinikum Regensburg DE Germany (DE)

How to cite

APA:

Freudenstein, D., Lippert, M., Popp, J.S., Aprato, J., Wegner, M., Sock, E.,... González Alvarado, M.N. (2023). Endogenous Sox8 is a critical factor for timely remyelination and oligodendroglial cell repletion in the cuprizone model. Scientific Reports, 13(1). https://dx.doi.org/10.1038/s41598-023-49476-5

MLA:

Freudenstein, David, et al. "Endogenous Sox8 is a critical factor for timely remyelination and oligodendroglial cell repletion in the cuprizone model." Scientific Reports 13.1 (2023).

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