Yin Chao, Zhang Meiya, Cheng Li, Ding Li, Lv Qing, Huang Zixuan, Zhou Jiaqi, Chen Jianmei, Wang Ping, Zhang Shunbo, You Qiuyun
School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
Engineering Research Center of TCM Protection Technology and New Product Development for the Elderly Brain Health, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, China.
Front Pharmacol. 2024 Jul 19;15:1430599. doi: 10.3389/fphar.2024.1430599. eCollection 2024.
Sleep deprivation (SD) is commonplace in today's fast-paced society. SD is a severe public health problem globally since it may cause cognitive decline and even neurodegenerative disorders like Alzheimer's disease. Melatonin (MT) is a natural chemical secreted by the pineal gland with neuroprotective effects. The purpose of this study was to investigate the protective effect and mechanism of MT on chronic sleep deprivation-induced cognitive impairment. A 3-week modified multi-platform method was used to create the SD rat model. The Morris water maze test (MWM), Tissue staining (including Hematoxylin and Eosin (H & E) staining, Nissl staining, and immunofluorescence), Western blot, Enzyme-linked immunosorbent assay (ELISA), and Quantitative real-time polymerase chain reaction (qPCR) were used to investigate the protective effect and mechanism of MT in ameliorating cognitive impairment in SD rats. The results showed that MT (50 and 100 mg/kg) significantly improved cognitive function in rats, as evidenced by a shortening of escape latency and increased time of crossing the platform and time spent in the quadrant. Additionally, MT therapy alleviated hippocampus neurodegeneration and neuronal loss while lowering levels of pathogenic factors (LPS) and inflammatory indicators (IL-1β, IL-6, TNF-α, iNOS, and COX2). Furthermore, MT treatment reversed the high expression of Aβ42 and Iba1 as well as the low expression of ZO-1 and occludin, and inhibited the SD-induced TLR4/MyD88/NF-κB signaling pathway. In summary, MT ameliorated spatial recognition and learning memory dysfunction in SD rats by reducing neuroinflammation and increasing neuroprotection while inhibiting the TLR4/MyD88/NF-κB signaling pathway. Our study supports the use of MT as an alternate treatment for SD with cognitive impairment.
睡眠剥夺（SD）在当今快节奏的社会中很常见。睡眠剥夺是一个严重的全球公共卫生问题，因为它可能导致认知能力下降，甚至引发如阿尔茨海默病等神经退行性疾病。褪黑素（MT）是松果体分泌的一种具有神经保护作用的天然化学物质。本研究的目的是探讨MT对慢性睡眠剥夺诱导的认知障碍的保护作用及其机制。采用为期3周的改良多平台法建立睡眠剥夺大鼠模型。通过莫里斯水迷宫试验（MWM）、组织染色（包括苏木精-伊红（H&E）染色、尼氏染色和免疫荧光）、蛋白质免疫印迹法、酶联免疫吸附测定（ELISA）和定量实时聚合酶链反应（qPCR），研究MT改善睡眠剥夺大鼠认知障碍的保护作用及其机制。结果表明，MT（50和100mg/kg）显著改善了大鼠的认知功能，表现为逃避潜伏期缩短、穿越平台时间增加以及在象限内停留时间延长。此外，MT治疗减轻了海马神经变性和神经元丢失，同时降低了致病因子（LPS）和炎症指标（IL-1β、IL-6、TNF-α、iNOS和COX2）的水平。此外，MT治疗逆转了Aβ42和Iba1的高表达以及ZO-1和闭合蛋白的低表达，并抑制了睡眠剥夺诱导的TLR4/MyD88/NF-κB信号通路。总之，MT通过减轻神经炎症、增强神经保护作用并抑制TLR4/MyD88/NF-κB信号通路，改善了睡眠剥夺大鼠的空间识别和学习记忆功能障碍。我们的研究支持将MT作为睡眠剥夺伴认知障碍的替代治疗方法。
