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

First Author  Freudenstein D Year  2023
Journal  Sci Rep Volume  13
Issue  1 Pages  22272
PubMed ID  38097655 Mgi Jnum  J:343511
Mgi Id  MGI:7566875 Doi  10.1038/s41598-023-49476-5
Citation  Freudenstein D, et al. (2023) Endogenous Sox8 is a critical factor for timely remyelination and oligodendroglial cell repletion in the cuprizone model. Sci Rep 13(1):22272
abstractText  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.
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