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  Neuronal cholesterol synthesis is essential for repair of chronically demyelinated lesions in mice

Berghoff, S. A., Spieth, L., Sun, T., Hosang, L., Depp, C., Sasmita, A. O., et al. (2021). Neuronal cholesterol synthesis is essential for repair of chronically demyelinated lesions in mice. Cell Reports, 37(4): 109889. doi:10.1016/j.celrep.2021.109889.

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 Creators:
Berghoff, S. A.1, Author           
Spieth, L.1, Author           
Sun, T.1, Author           
Hosang, L., Author
Depp, C.1, Author           
Sasmita, A. O.1, Author           
Vasileva, M. H.1, Author           
Scholz, P., Author
Zhao, Y., Author
Krüger, D.2, Author           
Wichert, S., Author
Brown, E. R., Author
Michail, K., Author
Nave, K.-A.1, Author           
Bonn, S., Author
Odoardi, F., Author
Rossner, M., Author
Ischebeck, T., Author
Edgar, J. M.1, Author           
Saher, G.1, Author           
Affiliations:
1Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society, ou_2173664              
2Molecular neurobiology, Max Planck Institute of Experimental Medicine, Max Planck Society, ou_2173659              

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Free keywords: EAE; OPC; cholesterol; cuprizone; demyelination; knockout; multiple sclerosis; myelin; neuron; oligodendrocyte.
 Abstract: Astrocyte-derived cholesterol supports brain cells under physiological conditions. However, in demyelin- ating lesions, astrocytes downregulate cholesterol synthesis, and the cholesterol that is essential for remye- lination has to originate from other cellular sources. Here, we show that repair following acute versus chronic demyelination involves distinct processes. In particular, in chronic myelin disease, when recycling of lipids is often defective, de novo neuronal cholesterol synthesis is critical for regeneration. By gene expression profiling, genetic loss-of-function experiments, and comprehensive phenotyping, we provide evidence that neurons increase cholesterol synthesis in chronic myelin disease models and in patients with multiple sclerosis (MS). In mouse models, neuronal cholesterol facilitates remyelination specifically by triggering oligodendrocyte precursor cell proliferation. Our data contribute to the understanding of disease progression and have implications for therapeutic strategies in patients with MS.

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Language(s): eng - English
 Dates: 2021-10-26
 Publication Status: Published online
 Pages: 11
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.celrep.2021.109889
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Project name : This work was funded by the Deutsche For- schungsgemeinschaft (SA 2014/2-1 to G.S.), the Wilhelm Sander-Stiftung (grant 2019.138.1 to G.S.), the Alzheimer Forschung Initiative (grant 19070 to G.S.), the UK MS Society (grant 127 to J.M.E.), the Adelson Medical Research Foundation (to K.A.N.), and Medical Research Scotland (PhD studentship 791- 2014 to E.R.B.).
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Title: Cell Reports
Source Genre: Journal
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Pages: - Volume / Issue: 37 (4) Sequence Number: 109889 Start / End Page: - Identifier: ISSN: 22111247