2020 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 study, we will perform comprehensive sleep analysis in CDD model mice. The results will significantly advance the knowledge about etiology and therapy of sleep disturbances in CDD.
In this year we have conducted sleep analysis in Cdkl5 knock-out (KO) mice, assessed sleep regulation of Cdkl5 KO mice, including sleep homeostasis and circadian function. In addition, we have generated conditional knockout (cKO) mice, in which the Cdkl5 gene is deleted in specific neurons.
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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 comprehensive sleep analysis in CDD model mice. The results are expected to be published in the next fiscal year (Cao et al. in preparation). We have produced several lines of CDD cKO mice, which 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 analyze sleep structures in different Cdkl5 cKO mouse lines to identify the neurons involved in sleep disturbance in CDD model mice. Also, 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 |
Some expensive reagents and materials for the experiments will be purchased in FY2021.
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[Journal Article] Thiazoline-related innate fear stimuli orchestrate hypothermia and anti-hypoxia via sensory TRPA1 activation2021
Author(s)
Tomohiko Matsuo, Tomoko Isosaka, Yuichiro Hayashi, Lijun Tang, Akihiro Doi, Aiko Yasuda, Mikio Hayashi, Chia-Ying Lee, Liqin Cao, Natsumaro Kutsuna, Sachihiro Matsunaga, Takeshi Matsuda, Ikuko Yao, Mitsuyoshi Setou, Dai Kanagawa, Koichiro Higasa, Masahito Ikawa, Qinghua Liu, Reiko Kobayakawa, Ko Kobayakawa
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Journal Title
Nature Communications
Volume: 12
Pages: 2074
DOI
Peer Reviewed / Open Access
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