Herein, we evaluated the neuroprotective effect of melatonin against cisplatin-induced oxidative damage, neuroinflammation, and synaptic dysfunction in mice. Cisplatin was administered at a dose of 2 mg/kg for eleven consecutive days to induce symptoms of cognitive impairment and neurodegeneration, while melatonin was administered at a 20 mg/kg dose for thirty consecutive days. We used various experimental techniques such as western blotting, immunofluorescence analysis, and oxidative stress marker assays to support our notion. Moreover, for cognitive impairment, we conducted behavioral analyses such as Morris Water Maze (MWM) and Y-Maze tests. The results indicated that melatonin attenuated oxidative stress by upregulating the expression of NF-E2–related factor-2 (Nrf2) dependent anti-oxidative protein levels. Similarly, melatonin positively modulated the expression of Sirt1 (a member of the sirtuin family), Phospho-AMPKα (Thr172), peroxisome proliferator-activated receptor (PPARγ), PPAR gamma coactivator 1 alpha (PGC-1α) coupled to downregulation of neuroinflammatory mediators and markers such as nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β). Moreover, melatonin significantly upregulated the expression of synaptic markers such as postsynaptic density protein -95 (PSD-95), synaptosomal-associated protein 23 (SNAP-23), and synaptophysin compared to the cisplatin alone group. Furthermore, the results of behavior tests suggested that melatonin significantly improved the cognitive functions of the cisplatin injected mice.

在此，我们评估了褪黑激素对顺铂诱导的小鼠氧化损伤、神经炎症和突触功能障碍的神经保护作用。顺铂以 2 mg/kg 的剂量连续 11 天施用，以诱导认知障碍和神经变性的症状，而褪黑激素以 20 mg/kg 的剂量连续 30 天施用。我们使用了各种实验技术，例如蛋白质印迹、免疫荧光分析和氧化应激标记物测定来支持我们的观点。此外，对于认知障碍，我们进行了莫里斯水迷宫（MWM）和Y-迷宫测试等行为分析。结果表明，褪黑激素通过上调 NF-E2 相关因子 2 (Nrf2) 依赖性抗氧化蛋白水平的表达来减轻氧化应激。同样，褪黑激素正向调节 Sirt1（sirtuin 家族成员）、Phospho-AMPKα (Thr172)、过氧化物酶体增殖物激活受体 (PPARγ)、PPAR γ 共激活剂 1 α (PGC-1α) 的表达，并下调神经炎症介质以及核因子κ-B (NF-κB)、肿瘤坏死因子-α (TNF-α) 和白细胞介素-1 β (IL-1β) 等标记物。此外，与单独使用顺铂组相比，褪黑激素显着​​上调突触标记物的表达，例如突触后密度蛋白-95 (PSD-95)、突触体相关蛋白23 (SNAP-23)和突触素。此外，行为测试结果表明，褪黑激素显着​​改善了注射顺铂的小鼠的认知功能。