Guo Wensheng, Mao Xin, Han Ding, Wang Hongqi, Zhang Wanning, Zhang Guitao, Zhang Ning, Nie Binbin, Li Hui, Song Yizhi, Wu Yan, Chang Lirong
Department of Anatomy, School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China.
Department of Neuropsychiatry and Behavioral Neurology and Clinical Psychology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Aging Brain. 2023 Aug 5;4:100091. doi: 10.1016/j.nbas.2023.100091. eCollection 2023.
For quite a long time, researches on Alzheimer's disease (AD) primarily focused on the cortex and hippocampus, while the cerebellum has been ignored because of its abnormalities considered to appear in the late stage of AD. In recent years, increasing evidence suggest that the cerebellar pathological changes possibly occur in the preclinical phase of AD, which is also associated with sleep disorder. Sleep disturbance is a high risk factor of AD. However, the changes and roles of cerebellum has rarely been reported under conditions of AD accompanied with sleep disorders. In this study, using an amyloid-β oligomers (AβO)-induced rat model of AD subjected to sleep deprivation, combining with a 7.0 T animals structural magnetic resonance imaging (MRI), we assessed structural changes of cerebellum in MRI. Our results showed that sleep deprivation combined with AβO led to an increased FA value in the anterior lobe of cerebellum, decreased ADC value in the cerebellar lobes and cerebellar nuclei, and increased cerebellum volume. Besides that, sleep deprivation exacerbated the damage of AβO to the cerebellar structural network. This study demonstrated that sleep deprivation could aggravate the damage to cerebellum induced by AβO. The present findings provide supporting evidence for the involvement of cerebellum in the early pathology of AD and sleep loss. Our data would contribute to advancing the understanding of the mysterious role of cerebellum in AD and sleep disorders, as well as would be helpful for developing non-invasive MRI biomarkers for screening early AD patients with self-reported sleep disturbances.
在相当长的一段时间里,对阿尔茨海默病(AD)的研究主要集中在大脑皮层和海马体,而小脑由于被认为在AD晚期才会出现异常而被忽视。近年来,越来越多的证据表明,小脑的病理变化可能发生在AD的临床前期,这也与睡眠障碍有关。睡眠障碍是AD的一个高风险因素。然而,在伴有睡眠障碍的AD情况下,小脑的变化和作用鲜有报道。在本研究中,我们使用淀粉样β寡聚体(AβO)诱导的AD大鼠睡眠剥夺模型,并结合7.0 T动物结构磁共振成像(MRI),评估了小脑在MRI中的结构变化。我们的结果显示睡眠剥夺与AβO共同作用导致小脑前叶的FA值增加,小脑叶和小脑核的ADC值降低以及小脑体积增大。除此之外,睡眠剥夺加剧了AβO对小脑结构网络的损伤。本研究表明睡眠剥夺会加重AβO对小脑的损伤。目前的研究结果为小脑参与AD早期病理过程和睡眠缺失提供了支持性证据。我们的数据将有助于推进对小脑在AD和睡眠障碍中神秘作用的理解,也有助于开发用于筛查有自我报告睡眠障碍的早期AD患者的非侵入性MRI生物标志物。