Elucidate the neural mechanisms underlying sleep disturbances in neurodevelopmental disorders-focusing on CDKL5 deficiency disorder-
| Project/Area Number |
20K06738
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 44050:Animal physiological chemistry, physiology and behavioral biology-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Cao Liqin 筑波大学, 国際統合睡眠医科学研究機構, 助教 (60399475)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | CDKL5 / 睡眠 / マウス / 神経発達障害 / 脳・神経 / 遺伝学 |
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| Outline of Research at the Start |
CDKL5 deficiency disorder (CDD) is a devastating neurodevelopmental disorder caused by pathogenic mutations in Cyclin-dependent kinase-like 5 (CDKL5) gene. More than 86% patients have severe sleep problems. However, little is known about the neuronal mechanism underlying the sleep disturbances in CDD patients. We will conduct comprehensive sleep analysis in Cdkl5 knockout (KO) mice by EEG and EMG recording, and identify neural circuitry responsible for sleep disturbances in Cdkl5 KO mice. The results will provide novel insight into the neuropathology of sleep disturbances in CDD.
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| Outline of Final Research Achievements |
CDKL5 deficiency disorder (CDD) is a devastating neurodevelopmental disorder caused by pathogenic mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene. The majority (>86%) of patients have severe sleep problems. However, little is known about the mechanism underlying sleep disturbances in CDD patients. In this study we conducted comprehensive sleep phenotyping in a Cdkl5 knockout (KO) mouse model by electroencephalography (EEG) and electromyography (EMG) recording. Cdkl5 KO mice spent less time in non-rapid eye movement sleep and more time awake over a 24-hour period, and showed shorter sleep episode duration compared to their wild-type littermates. Moreover, Cdkl5 KO mice exhibited abnormality in EEG power spectrum. These features in Cdkl5 KO mice are consistent with the sleep patterns and abnormal EEG observed in patients with CDD.
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| Academic Significance and Societal Importance of the Research Achievements |
We performed for the first time the comprehensive sleep characterization of Cdkl5 KO mice. Cdkl5 KO mice recapitulate sleep disturbances and background EEG abnormality in patients with CDD, suggesting that Cdkl5 KO mice can be a good genetic model to study sleep disturbances in CDD.
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Report
(4 results)
Research Products
(9 results)
