Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, China.
Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, China; Dongguan Seventh People's Hospital (Dongguan Mental Health Center), Dongguan, China.
Behav Brain Res. 2024 Jul 26;470:115067. doi: 10.1016/j.bbr.2024.115067. Epub 2024 May 23.
Sleep disorders, depression, and Alzheimer's disease (AD) are extensively reported as comorbidity. Although neuroinflammation triggered by microglial phenotype M1 activation, leading to neurotransmitter dysfunction and Aβ aggregation, is considered as the leading cause of depression and AD, whether and how sub-chronic or chronic sleep deprivation (SD) contribute to the onset and development of these diseases remains unclear.
Memory and depression-like behaviors were evaluated in both SDs, and then circadian markers, glial cell phenotype polarization, cytokines, depression-related neurotransmitters, and AD-related gene/protein expressions were measured by qRT-PCR, enzyme-linked immunosorbent assay, high-performance liquid chromatography, and western-blotting respectively.
Both SDs induced give-up behavior and anhedonia and increased circadian marker period circadian regulator 2 (PER2) expression, which were much worse in chronic than in the sub-chronic SD group, while brain and muscle ARNT-like protein-1 only decreased in the chronic-SD. Furthermore, increased microglial M1 and astrocyte A1 expression and proinflammatory cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α was observed in both SDs, which were more significant in chronic SD. Similarly, decreased norepinephrine and 5-hydroxytryptamine/5-hydroxyindoleacetic acid ratio were more significant, which corresponds to the worse depression-like behavior in chronic than sub-chronic-SD. With regard to AD, increased amyloid precursor protein (APP) and soluble (s)-APPβ and decreased sAPPα in both SDs were more significant in the chronic. However, sAPPα/sAPPβ ratio was only decreased in chronic SD.
These findings suggest that both SDs induce depression-like changes by increasing PER2, leading to neuroinflammation and neurotransmitter dysfunction. However, only chronic SD induced memory impairment likely due to severer circadian disruption, higher neuroinflammation, and dysregulation of APP metabolism.
睡眠障碍、抑郁和阿尔茨海默病（AD）被广泛报道为共病。尽管微胶质细胞表型 M1 激活引发的神经炎症导致神经递质功能障碍和 Aβ 聚集被认为是抑郁和 AD 的主要原因，但亚慢性或慢性睡眠剥夺（SD）是否以及如何导致这些疾病的发生和发展仍不清楚。
在 SD 后评估记忆和抑郁样行为，然后通过 qRT-PCR、酶联免疫吸附试验、高效液相色谱和 Western-blotting 分别测量神经胶质细胞表型极化、细胞因子、抑郁相关神经递质和 AD 相关基因/蛋白的表达。
两种 SD 均导致放弃行为和快感缺失，并增加昼夜节律标记物周期节律调节因子 2（PER2）的表达，慢性 SD 比亚慢性 SD 更严重，而脑和肌肉 ARNT 样蛋白-1 仅在慢性-SD 中降低。此外，两种 SD 均观察到小胶质细胞 M1 和星形胶质细胞 A1 表达增加和促炎细胞因子白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子-α增加，慢性 SD 更显著。同样，去甲肾上腺素和 5-羟色胺/5-羟吲哚乙酸比值降低更显著，对应于慢性 SD 中更严重的抑郁样行为。关于 AD，两种 SD 均增加淀粉样前体蛋白（APP）和可溶性（s）-APPβ，而慢性 SD 中降低 sAPPα。然而，只有慢性 SD 中 sAPPα/sAPPβ 比值降低。
这些发现表明，两种 SD 通过增加 PER2 诱导抑郁样变化，导致神经炎症和神经递质功能障碍。然而，只有慢性 SD 引起记忆障碍，可能是由于更严重的昼夜节律紊乱、更高的神经炎症和 APP 代谢失调。
