Wei Ru-Meng, Zhang Meng-Ying, Fang Shi-Kun, Liu Gao-Xia, Hu Fei, Li Xue-Yan, Zhang Kai-Xuan, Zhang Jing-Ya, Liu Xue-Chun, Zhang Yue-Ming, Chen Gui-Hai
Department of Neurology (sleep disorders), the Affiliated Chaohu Hospital of Anhui Medical University, Hefei, Anhui 238001, PR China.
Department of Anesthesiology, the Affiliated Chaohu Hospital of Anhui Medical University, Hefei, Anhui 238001, PR China.
Psychoneuroendocrinology. 2025 Jan;171:107210. doi: 10.1016/j.psyneuen.2024.107210. Epub 2024 Oct 5.
Intermittent hypoxia (IH), a major pathophysiologic alteration in obstructive sleep apnea syndrome (OSAS), is an important contributor to cognitive impairment. Increasing research suggests that melatonin has anti-inflammatory properties and improves functions related to synaptic plasticity. However, it is unclear whether melatonin has a protective effect against OSAS-induced cognitive dysfunction in aged individuals and the involved mechanisms are also unclear. Therefore, in the study, the effects of exposure to IH alone and IH in combination with daily melatonin treatment were investigated in C57BL/6 J mice aged 18 months. Assessment of the cognitive ability of mice in a Morris water maze showed that melatonin attenuated IH-induced impairment of learning and memory in aged mice. Enzyme-linked immunosorbent assay, polymerase chain reaction, and western blotting molecular techniques showed that melatonin treatment reduced the levels of the proinflammatory cytokines, interleukin-1β, interleukin-6, and tumor necrosis factor-α, decreased the levels of NOD-like receptor thermal protein domain associated protein 3 and nuclear factor kappa-B, lowered the levels of ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein, and increased the levels of the synaptic proteins, activity-regulated cytoskeleton-associated protein, growth-associated protein-43, postsynaptic density protein 95, and synaptophysin in IH-exposed mice. Moreover, electrophysiological results showed that melatonin ameliorated the decline in long-term potentiation induced by IH. The results suggest that melatonin can ameliorate IH-induced cognitive deficits by inhibiting neuroinflammation and improving synaptic plasticity in aged mice.
间歇性缺氧（IH）是阻塞性睡眠呼吸暂停综合征（OSAS）的主要病理生理改变，是认知障碍的重要促成因素。越来越多的研究表明，褪黑素具有抗炎特性，并能改善与突触可塑性相关的功能。然而，尚不清楚褪黑素对老年个体OSAS诱导的认知功能障碍是否具有保护作用，其相关机制也不清楚。因此，在本研究中，我们在18个月大的C57BL/6 J小鼠中研究了单独暴露于IH以及IH与每日褪黑素治疗联合应用的效果。通过莫里斯水迷宫对小鼠认知能力的评估表明，褪黑素减轻了IH诱导的老年小鼠学习和记忆障碍。酶联免疫吸附测定、聚合酶链反应和蛋白质印迹分子技术表明，褪黑素治疗降低了促炎细胞因子白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α的水平，降低了NOD样受体热蛋白结构域相关蛋白3和核因子κB的水平，降低了离子钙结合衔接分子1和胶质纤维酸性蛋白的水平，并增加了暴露于IH的小鼠中突触蛋白、活性调节细胞骨架相关蛋白、生长相关蛋白-43、突触后致密蛋白95和突触素的水平。此外，电生理结果表明，褪黑素改善了IH诱导的长期增强作用的下降。结果表明，褪黑素可以通过抑制神经炎症和改善老年小鼠的突触可塑性来减轻IH诱导的认知缺陷。
