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

Stefan A Berghoff; Lena Spieth; Ting Sun; Leon Hosang; Constanze Depp; Andrew O Sasmita; Martina H Vasileva; Patricia Scholz; Yu Zhao; Dilja Krueger-Burg; Sven Wichert; Euan R Brown; Kyriakos Michail; Klaus-Armin Nave; Stefan Bonn; Francesca Odoardi; Moritz Rossner; Till Ischebeck; Julia M Edgar; Gesine Saher

doi:10.1016/j.celrep.2021.109889

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

Standard

Neuronal cholesterol synthesis is essential for repair of chronically demyelinated lesions in mice. / Berghoff, Stefan A; Spieth, Lena; Sun, Ting; Hosang, Leon; Depp, Constanze; Sasmita, Andrew O; Vasileva, Martina H; Scholz, Patricia; Zhao, Yu; Krueger-Burg, Dilja; Wichert, Sven; Brown, Euan R; Michail, Kyriakos; Nave, Klaus-Armin; Bonn, Stefan; Odoardi, Francesca; Rossner, Moritz; Ischebeck, Till; Edgar, Julia M; Saher, Gesine.

in: CELL REP, Jahrgang 37, Nr. 4, 109889, 26.10.2021.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Berghoff, SA, Spieth, L, Sun, T, Hosang, L, Depp, C, Sasmita, AO, Vasileva, MH, Scholz, P, Zhao, Y, Krueger-Burg, D, Wichert, S, Brown, ER, Michail, K, Nave, K-A, Bonn, S, Odoardi, F, Rossner, M, Ischebeck, T, Edgar, JM & Saher, G 2021, 'Neuronal cholesterol synthesis is essential for repair of chronically demyelinated lesions in mice', CELL REP, Jg. 37, Nr. 4, 109889. https://doi.org/10.1016/j.celrep.2021.109889

APA

Berghoff, S. A., Spieth, L., Sun, T., Hosang, L., Depp, C., Sasmita, A. O., Vasileva, M. H., Scholz, P., Zhao, Y., Krueger-Burg, D., Wichert, S., Brown, E. R., Michail, K., Nave, K-A., Bonn, S., Odoardi, F., Rossner, M., Ischebeck, T., Edgar, J. M., & Saher, G. (2021). Neuronal cholesterol synthesis is essential for repair of chronically demyelinated lesions in mice. CELL REP, 37(4), [109889]. https://doi.org/10.1016/j.celrep.2021.109889

Vancouver

Berghoff SA, Spieth L, Sun T, Hosang L, Depp C, Sasmita AO et al. Neuronal cholesterol synthesis is essential for repair of chronically demyelinated lesions in mice. CELL REP. 2021 Okt 26;37(4). 109889. https://doi.org/10.1016/j.celrep.2021.109889

Bibtex

@article{b7fac64189584e4a814adcac86d920ac,

title = "Neuronal cholesterol synthesis is essential for repair of chronically demyelinated lesions in mice",

abstract = "Astrocyte-derived cholesterol supports brain cells under physiological conditions. However, in demyelinating lesions, astrocytes downregulate cholesterol synthesis, and the cholesterol that is essential for remyelination 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.",

author = "Berghoff, {Stefan A} and Lena Spieth and Ting Sun and Leon Hosang and Constanze Depp and Sasmita, {Andrew O} and Vasileva, {Martina H} and Patricia Scholz and Yu Zhao and Dilja Krueger-Burg and Sven Wichert and Brown, {Euan R} and Kyriakos Michail and Klaus-Armin Nave and Stefan Bonn and Francesca Odoardi and Moritz Rossner and Till Ischebeck and Edgar, {Julia M} and Gesine Saher",

year = "2021",

month = oct,

day = "26",

doi = "10.1016/j.celrep.2021.109889",

language = "English",

volume = "37",

journal = "CELL REP",

issn = "2211-1247",

publisher = "Elsevier",

number = "4",

}

RIS

TY - JOUR

T1 - Neuronal cholesterol synthesis is essential for repair of chronically demyelinated lesions in mice

AU - Berghoff, Stefan A

AU - Spieth, Lena

AU - Sun, Ting

AU - Hosang, Leon

AU - Depp, Constanze

AU - Sasmita, Andrew O

AU - Vasileva, Martina H

AU - Scholz, Patricia

AU - Zhao, Yu

AU - Krueger-Burg, Dilja

AU - Wichert, Sven

AU - Brown, Euan R

AU - Michail, Kyriakos

AU - Nave, Klaus-Armin

AU - Bonn, Stefan

AU - Odoardi, Francesca

AU - Rossner, Moritz

AU - Ischebeck, Till

AU - Edgar, Julia M

AU - Saher, Gesine

PY - 2021/10/26

Y1 - 2021/10/26

N2 - Astrocyte-derived cholesterol supports brain cells under physiological conditions. However, in demyelinating lesions, astrocytes downregulate cholesterol synthesis, and the cholesterol that is essential for remyelination 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.

AB - Astrocyte-derived cholesterol supports brain cells under physiological conditions. However, in demyelinating lesions, astrocytes downregulate cholesterol synthesis, and the cholesterol that is essential for remyelination 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.

U2 - 10.1016/j.celrep.2021.109889

DO - 10.1016/j.celrep.2021.109889

M3 - SCORING: Journal article

C2 - 34706227

VL - 37

JO - CELL REP

JF - CELL REP

SN - 2211-1247

IS - 4

M1 - 109889

ER -