PDF(Pubmed)
Abstract：
BACKGROUND: Cryptochrome-2 (CRY2) is a core rhythm gene that plays a crucial role in DNA damage repair. The present study investigated the potential role of CRY2 in mediating sleep deprivation-induced cognitive decline in 5xFAD mice.
METHODS: To assess the effects of SD on different brain regions of the mouse brain, we used 18F FDG PET-CT. Cognitive function was evaluated using the Morris water maze test and Y-maze. Lentivirus was used for the overexpression of CRY2, and small interfering RNA (siRNA) was used for the downregulation of CRY2 to verify the effect of CRY2. We used qRT‒PCR and Western blotting to identify the downstream factors of CRY2 and evaluated the cognitive function of mice to confirm the effects of these factors.
RESULTS: The AD mice exhibited cognitive decline after 21 days of SD and had higher expression of CRY2 compared to AD mice with normal sleep. Overexpression of CRY2 led to decreased cognitive function in AD mice, and the downregulation of CRY2 attenuated the SD-induced cognitive decline in AD mice. CRY2 reduced the expression and function of CISH, which reduced the inhibition of STAT1 phosphorylation and led to synaptic dysfunction. CISH overexpression attenuated the impairing effect of sleep deprivation on cognitive function in AD mice. Furthermore, 18F FDG PET-CT revealed that SD significantly reduced glucose metabolism in different brain regions of AD mice.
CONCLUSIONS: Our study demonstrated that sleep deprivation upregulated CRY2 in the hippocampus of AD mice, which resulted in synaptic dysfunction by decreasing CISH-mediated STAT1 phosphorylation.
METHODS: To assess the effects of SD on different brain regions of the mouse brain, we used 18F FDG PET-CT. Cognitive function was evaluated using the Morris water maze test and Y-maze. Lentivirus was used for the overexpression of CRY2, and small interfering RNA (siRNA) was used for the downregulation of CRY2 to verify the effect of CRY2. We used qRT‒PCR and Western blotting to identify the downstream factors of CRY2 and evaluated the cognitive function of mice to confirm the effects of these factors.
RESULTS: The AD mice exhibited cognitive decline after 21 days of SD and had higher expression of CRY2 compared to AD mice with normal sleep. Overexpression of CRY2 led to decreased cognitive function in AD mice, and the downregulation of CRY2 attenuated the SD-induced cognitive decline in AD mice. CRY2 reduced the expression and function of CISH, which reduced the inhibition of STAT1 phosphorylation and led to synaptic dysfunction. CISH overexpression attenuated the impairing effect of sleep deprivation on cognitive function in AD mice. Furthermore, 18F FDG PET-CT revealed that SD significantly reduced glucose metabolism in different brain regions of AD mice.
CONCLUSIONS: Our study demonstrated that sleep deprivation upregulated CRY2 in the hippocampus of AD mice, which resulted in synaptic dysfunction by decreasing CISH-mediated STAT1 phosphorylation.
摘要：
背景：隐色素-2（CRY2）是一种核心节律基因，在DNA损伤修复中起着至关重要的作用。本研究调查了CRY2在5xFAD小鼠中介导睡眠剥夺引起的认知下降中的潜在作用。
方法：为了评估SD对小鼠大脑不同脑区的影响，我们使用18FFDGPET-CT。使用Morris水迷宫测试和Y迷宫评估认知功能。慢病毒用于过表达CRY2,小干扰RNA(siRNA)用于下调CRY2以验证CRY2的作用。我们使用qRT-PCR和Western印迹来鉴定CRY2的下游因子，并评估小鼠的认知功能以确认这些因子的影响。
结果：与睡眠正常的AD小鼠相比，AD小鼠在SD21天后表现出认知能力下降，并且CRY2的表达更高。过表达CRY2导致AD小鼠认知功能下降,CRY2的下调减轻了SD诱导的AD小鼠认知功能下降。CRY2降低CISH的表达和功能，这减少了对STAT1磷酸化的抑制并导致突触功能障碍。CISH过表达减轻了睡眠剥夺对AD小鼠认知功能的损害作用。此外，18FFDGPET-CT显示SD显著降低AD小鼠不同脑区的糖代谢。
结论：我们的研究表明，睡眠剥夺可上调AD小鼠海马中的CRY2，通过降低CISH介导的STAT1磷酸化导致突触功能障碍。
方法：为了评估SD对小鼠大脑不同脑区的影响，我们使用18FFDGPET-CT。使用Morris水迷宫测试和Y迷宫评估认知功能。慢病毒用于过表达CRY2,小干扰RNA(siRNA)用于下调CRY2以验证CRY2的作用。我们使用qRT-PCR和Western印迹来鉴定CRY2的下游因子，并评估小鼠的认知功能以确认这些因子的影响。
结果：与睡眠正常的AD小鼠相比，AD小鼠在SD21天后表现出认知能力下降，并且CRY2的表达更高。过表达CRY2导致AD小鼠认知功能下降,CRY2的下调减轻了SD诱导的AD小鼠认知功能下降。CRY2降低CISH的表达和功能，这减少了对STAT1磷酸化的抑制并导致突触功能障碍。CISH过表达减轻了睡眠剥夺对AD小鼠认知功能的损害作用。此外，18FFDGPET-CT显示SD显著降低AD小鼠不同脑区的糖代谢。
结论：我们的研究表明，睡眠剥夺可上调AD小鼠海马中的CRY2，通过降低CISH介导的STAT1磷酸化导致突触功能障碍。
