Abstract
AbstractSleep behavior is conserved throughout evolution, and sleep disturbances are a frequent comorbidity of neuropsychiatric disorders. However, the molecular basis underlying sleep dysfunctions in neurological diseases remains elusive. Using a model for neurodevelopmental disorders (NDDs), theDrosophila Cytoplasmic FMR1 interacting proteinhaploinsufficiency (Cyfip85.1/+), we identify a mechanism modulating sleep homeostasis. We show that increased activity of the sterol regulatory element-binding protein (SREBP) inCyfip85.1/+flies induces an increase in the transcription of wakefulness-associated genes, such as the malic enzyme (Men), causing a disturbance in the daily NADP+/NADPH ratio oscillations and reducing sleep pressure at the night-time onset. Reduction in SREBP or Men activity inCyfip85.1/+flies enhances the NADP+/NADPH ratio and rescues the sleep deficits, indicating that SREBP and Men are causative for the sleep deficits inCyfipheterozygous flies. This work suggests modulation of the SREBP metabolic axis as a new avenue worth exploring for its therapeutic potential in sleep disorders.
Funder
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Katholieke Universiteit Leuven | Universitaire Ziekenhuizen Leuven, KU Leuven
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Cited by
3 articles.
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