RRC ID 70777
著者 Coll-Tané M, Gong NN, Belfer SJ, van Renssen LV, Kurtz-Nelson EC, Szuperak M, Eidhof I, van Reijmersdal B, Terwindt I, Durkin J, Verheij MMM, Kim CN, Hudac CM, Nowakowski TJ, Bernier RA, Pillen S, Earl RK, Eichler EE, Kleefstra T, Kayser MS, Schenck A.
タイトル The CHD8/CHD7/Kismet family links blood-brain barrier glia and serotonin to ASD-associated sleep defects.
ジャーナル Sci Adv
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.
巻・号 7(23)
公開日 2021-6-1
DOI 10.1126/sciadv.abe2626
PII 7/23/eabe2626
PMID 34088660
PMC PMC8177706
MeSH Animals Autistic Disorder* / genetics Blood-Brain Barrier / metabolism DNA Helicases / metabolism DNA-Binding Proteins* / metabolism Drosophila / metabolism Neuroglia / metabolism Quality of Life Serotonin Sleep Transcription Factors / metabolism
IF 13.117
リソース情報
ショウジョウバエ DGRC#113173 DGRC#105240 DGRC#112830 DGRC#112853