Elucidate the neural mechanisms underlying sleep disturbances in neurodevelopmental disorders-focusing on CDKL5 deficiency disorder-

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06738
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44050:Animal physiological chemistry, physiology and behavioral biology-related
• Research Institution: University of Tsukuba
• Principal Investigator: Cao Liqin 筑波大学, 国際統合睡眠医科学研究機構, 助教 (60399475)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: CDKL5 / 睡眠 / マウス / 神経発達障害 / 脳・神経 / 遺伝学

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.

Free Research Field

動物生理化学、生理学および行動学関連

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.