Department of Pediatric, Chongqing University Fuling Hospital, Chongqing, China.
Institute of Neuroscience, Department of Physiology, School of Basic Medical Science, Chongqing Medical University, Chongqing, China.
Brain Behav. 2023 Jul;13(7):e3075. doi: 10.1002/brb3.3075. Epub 2023 May 24.
Sleep abnormalities are highly correlated with neurodevelopmental disorders, such as intellectual disability, attention deficit hyperactivity disorder, and autism spectrum disorders (ASD). The severity of behavioral abnormalities is correlated with the presence of sleep abnormalities. Based on previous research, we investigated that Ctnnd2 gene deletion in mice lead to ASD-like behaviors and cognitive defects. Given the importance of sleep in individuals with ASD, this study aimed to determine the effects of chronic sleep restriction (SR) on wild-type (WT) mice and on Ctnnd2 deletion-induced, neurologically related phenotypes in mice.
WT and Ctnnd2 knockout (KO) mice were both subjected to manual SR (5 h per day) for 21 consecutively days separately, then we compared neurologically related phenotypes of WT mice, WT mice subjected to SR, KO mice, and KO mice subjected to SR using a three-chamber assay, direct social interaction test, open-field test, Morris water maze, Golgi staining, and Western blotting.
The effects of SR on WT and KO mice were different. After SR, social ability and cognition were impaired in both WT and KO mice. Repetitive behaviors were increased, and exploration abilities were decreased in KO mice but not in WT mice. Moreover, SR reduced the density and area of mushroom-type dendritic spines in WT rather than KO mice. Finally, the PI3K/Akt-mTOR pathway was found to be involved in the effects induced by SR-impaired phenotypes in WT and KO mice.
Overall, results of the present study may have implications for the role of disrupted sleep in patients with CTNND2 gene-related autism and the evolution of neurodevelopmental disorders.
睡眠异常与神经发育障碍高度相关，例如智力障碍、注意缺陷多动障碍和自闭症谱系障碍（ASD）。行为异常的严重程度与睡眠异常的存在相关。基于之前的研究，我们发现 Ctnnd2 基因缺失的小鼠会出现类似 ASD 的行为和认知缺陷。鉴于睡眠对于 ASD 患者的重要性，本研究旨在确定慢性睡眠限制（SR）对野生型（WT）小鼠以及 Ctnnd2 缺失诱导的与神经相关表型的小鼠的影响。
WT 和 Ctnnd2 敲除（KO）小鼠分别接受手动 SR（每天 5 小时）21 天，然后使用三箱试验、直接社交互动测试、旷场试验、Morris 水迷宫、高尔基染色和 Western blot 比较 WT 小鼠、接受 SR 的 WT 小鼠、KO 小鼠和接受 SR 的 KO 小鼠的神经相关表型。
SR 对 WT 和 KO 小鼠的影响不同。在 SR 之后，WT 和 KO 小鼠的社交能力和认知能力都受损。重复行为增加，而 KO 小鼠的探索能力下降，但 WT 小鼠没有。此外，SR 减少了 WT 而不是 KO 小鼠中蘑菇型树突棘的密度和面积。最后，发现 PI3K/Akt-mTOR 通路参与了 SR 引起的 WT 和 KO 小鼠表型受损的作用。
总的来说，本研究的结果可能对 CTNND2 基因相关自闭症患者睡眠中断的作用以及神经发育障碍的演变具有启示意义。
