Sleep loss induces cholesterol-associated myelin dysfunction
Abstract
The increasing prevalence of sleep deprivation poses a public health challenge in modern society. Manifestations of reduced alertness, such as slowed reaction times and increased errors, are well-documented behavioral indicators of sleep loss (SL). Yet, the biological consequences of sleep deprivation and their role in behavioral impairment remain elusive. Our study reveals significant effects of sleep deprivation on myelin integrity. As a result, we identify increased conduction delays in nerve signal propagation, hindered interhemispheric synchronization, and impaired cognitive and motor performance associated with SL. By profiling oligodendrocyte transcriptome and lipidome, we observe SL-induced endoplasmic reticulum stress and lipid metabolism dysregulation, particularly affecting cholesterol homeostasis. Boosting cholesterol transport to myelin sheaths prevents SL effects on nerve signal propagation and behavior. Our findings highlight a possible role of oligodendrocyte cholesterol dysregulation in behavioral deficits associated with SL and unveil a novel target for intervention.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (14)
Reyila Simayi
School of Pharmacy, University of Camerino
Eleonora Ficiarà
School of Pharmacy, University of Camerino
Oluwatomisin Faniyan
Center for Neuroscience, University of Camerino
Antonio Cerdán Cerdá
Instituto de Neurociencias (Consejo Superior de Investigaciones Científicas - Universidad Miguel Hernández)
Amina Aboufares El Alaoui
Center for Neuroscience, University of Camerino
Rosamaria Fiorini
Department of Life and Environmental Sciences, Marche Polytechnic University
Adele Cutignano
Istituto di Chimica Biomolecolare–Consiglio Nazionale delle Ricerche
Fabiana Piscitelli
Istituto di Chimica Biomolecolare–Consiglio Nazionale delle Ricerche
Aroa S. Maroto
Instituto de Neurociencias (Consejo Superior de Investigaciones Científicas - Universidad Miguel Hernández)
Alexandra Santos
Instituto de Neurociencias (Consejo Superior de Investigaciones Científicas - Universidad Miguel Hernández)
Federico Del Gallo
School of Pharmacy, University of Camerino
Luisa de Vivo
School of Pharmacy, University of Camerino
Silvia De Santis
Instituto de Neurociencias (Consejo Superior de Investigaciones Científicas - Universidad Miguel Hernández)
Michele Bellesi
Center for Neuroscience, University of Camerino