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Coll-TanĂ©, M., Gong, N.N., Belfer, S.J., van Renssen, L.V., Kurtz-Nelson, E.C., Szuperak, M., Eidhof, I., van Reijmersdal, B., Terwindt, I., Durkin, J., Verheij, M.M.M., Kim, C.N., Hudac, C.M., Nowakowski, T.J., Bernier, R.A., Pillen, S., Earl, R.K., Eichler, E.E., Kleefstra, T., Kayser, M.S., Schenck, A. (2021). The CHD8/CHD7/Kismet family links blood-brain barrier glia and serotonin to ASD-associated sleep defects.  Sci. Adv. 7(23): eabe2626.
FlyBase ID
FBrf0249177
Publication Type
Research paper
Abstract

Sleep disturbances in autism and neurodevelopmental disorders are common and adversely affect patient's quality of life, yet the underlying mechanisms are understudied. We found that individuals with mutations in CHD8, among the highest-confidence autism risk genes, or CHD7 suffer from disturbed sleep maintenance. These defects are recapitulated in Drosophila mutants affecting kismet, the sole CHD8/CHD7 ortholog. We show that Kismet is required in glia for early developmental and adult sleep architecture. This role localizes to subperineurial glia constituting the blood-brain barrier. We demonstrate that Kismet-related sleep disturbances are caused by high serotonin during development, paralleling a well-established but genetically unsolved autism endophenotype. Despite their developmental origin, Kismet's sleep architecture defects can be reversed in adulthood by a behavioral regime resembling human sleep restriction therapy. Our findings provide fundamental insights into glial regulation of sleep and propose a causal mechanistic link between the CHD8/CHD7/Kismet family, developmental hyperserotonemia, and autism-associated sleep disturbances.

PubMed ID
PubMed Central ID
PMC8177706 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Sci. Adv.
    Title
    Science advances
    ISBN/ISSN
    2375-2548
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