RESUMO
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.
Assuntos
Fatores de Transcrição ARNTL , Esclerose Múltipla , Camundongos , Animais , Fatores de Transcrição ARNTL/genética , Privação do Sono/metabolismo , Camundongos Knockout , Oligodendroglia/metabolismo , Bainha de Mielina/metabolismo , Esclerose Múltipla/metabolismo , Sono/genética , Diferenciação CelularRESUMO
Limited data are available on the clinical presentation and outcomes of coronavirus disease (COVID-19) patients in the United States hospitalized under normal-caseload or nonsurge conditions. We retrospectively studied 72 consecutive adult patients hospitalized with COVID-19 in 2 hospitals in the San Francisco Bay area, California, USA, during March 13-April 11, 2020. The death rate for all hospitalized COVID-19 patients was 8.3%, and median length of hospitalization was 7.5 days. Of the 21 (29% of total) intensive care unit patients, 3 (14.3% died); median length of intensive care unit stay was 12 days. Of the 72 patients, 43 (59.7%) had underlying cardiovascular disease and 19 (26.4%) had underlying pulmonary disease. In this study, death rates were lower than those reported from regions of the United States experiencing a high volume of COVID-19 patients.