2021 Fiscal Year Research-status Report
Elucidate the neural mechanisms underlying sleep disturbances in neurodevelopmental disorders-focusing on CDKL5 deficiency disorder-
| Project/Area Number |
20K06738
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| Research Institution | University of Tsukuba |
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Principal Investigator |
曹 麗琴 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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| 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 Annual Research Achievements |
CDKL5 deficiency disorder (CDD) is a devastating X-linked neurodevelopmental disorder caused by pathogenic mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene. The majority (>86%) of patients have severe sleep problems, which greatly affect the quality of life for patients and their families. However, little is known about the neuronal mechanism underlying the sleep disturbances in CDD patients.
In this year we have performed sleep analysis for juvenile and aged Cdkl5 knock-out (KO) mice. The results enable to understand the natural history of sleep disturbances in CDD mouse model and facilitate developing therapeutic strategy for treating sleep problems in CDD. We have also analysed sleep phenotypes of Cdkl5 conditional knockout (cKO) mice, which allows us to dissect the neural circuits responsible for sleep disruptions in CDD.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
We have finished the natural history of sleep disturbances in CDD mice. We will submit the manuscript for publication in this year (Cao et al. in preparation). We have produced and analyzed sleep phenotypes in several lines of Cdkl5 cKO mice, the results will allow us to identify neural mechanisms underlying sleep disturbances in CDD model mice.
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| Strategy for Future Research Activity |
We will perform whole-brain c-fos staining at different zeitgeber times in Cdkl5 cKO and wild-type mice to identify the brain regions and neural circuits critical for sleep disruptions in CDD.
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| Causes of Carryover |
ome expensive reagents and materials for the experiments will be purchased in FY2022.
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