BMAL1 loss in oligodendroglia contributes to abnormal myelination and sleep

被引：20

作者：

Rojo, Daniela ^{[1
]}

Dal Cengio, Louisa ^{[1
]}

Badner, Anna ^{[1
]}

Kim, Samuel ^{[1
]}

Sakai, Noriaki ^{[1
]}

Greene, Jacob ^{[1
]}

Dierckx, Tess ^{[1
]}

Mehl, Lindsey C. ^{[1
,2
]}

Eisinger, Ella ^{[1
]}

Ransom, Julia ^{[1
]}

Arellano-Garcia, Caroline ^{[1
,3
]}

Gumma, Mohammad E. ^{[1
]}

Soyk, Rebecca L. ^{[1
]}

Lewis, Cheyanne M. ^{[4
]}

Lam, Mable ^{[5
]}

Weigel, Maya K. ^{[5
,6
]}

Damonte, Valentina Martinez ^{[1
]}

Yalcin, Belgin ^{[7
]}

Jones, Samuel E. ^{[8
]}

Ollila, Hanna M. ^{[8
,9
,10
,11
,12
]}

Nishino, Seiji ^{[1
]}

Gibson, Erin M. ^{[1
]}

机构：

[1] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Palo Alto, CA 94305 USA

[2] Stanford Univ, Canc Biol Grad Program, Sch Med, Palo Alto, CA 94305 USA

[3] Stanford Univ, BioX Program, Palo Alto, CA 94305 USA

[4] Stanford Univ, Neurosci Grad Program, Palo Alto, CA 94305 USA

[5] Stanford Univ, Dept Neurosurg, Sch Med, Palo Alto, CA 94305 USA

[6] Stanford Univ, Stem Cell Biol & Regenerat Med Program, Sch Med, Palo Alto, CA 94305 USA

[7] Stanford Univ, Dept Neurol & Neurol Sci, Sch Med, Palo Alto, CA 94305 USA

[8] Univ Helsinki, Inst Mol Med, HiLIFE, Helsinki 00014, Finland

[9] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[10] Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA

[11] Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA

[12] Harvard Med Sch, Boston, MA 02114 USA

来源：

NEURON | 2023年 / 111卷 / 22期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

MENDELIAN RANDOMIZATION; PROGENITOR CELLS; CIRCADIAN CLOCK; GENETIC-VARIANTS; MIGRATION; DIFFERENTIATION; REMYELINATION; ARCHITECTURE; AGENESIS; IMPACT;

D O I：

10.1016/j.neuron.2023.08.002

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Myelination depends on the maintenance of oligodendrocytes that arise from oligodendrocyte precursor cells (OPCs). We show that OPC-specific proliferation, morphology, and BMAL1 are time -of -day dependent. Knockout of Bmal1 in mouse OPCs during development disrupts the expression of genes associated with circadian rhythms, proliferation, density, morphology, and migration, leading to changes in OPC dynamics in a spatiotemporal manner. Furthermore, these deficits translate into thinner myelin, dysregulated cognitive and motor functions, and sleep fragmentation. OPC-specific Bmal1 loss in adulthood does not alter OPC density at baseline but impairs the remyelination of a demyelinated lesion driven by changes in OPC morphology and migration. Lastly, we show that sleep fragmentation is associated with increased prevalence of the demyelinating disorder multiple sclerosis (MS), suggesting a link between MS and sleep that requires further investigation. These findings have broad mechanistic and therapeutic implications for brain disorders that include both myelin and sleep phenotypes.

引用

页码：3604 / +

页数：27

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