論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 45 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ショウジョウバエ | DGRC#113173 DGRC#105240 DGRC#112830 DGRC#112853 |