褪黑素可减轻顺铂引起的大鼠认知障碍并改善海马树突棘密度。
Melatonin mitigates cisplatin-induced cognitive impairment in rats and improves hippocampal dendritic spine density.
发表日期:2024 Jul 01
作者:
Shahd Qutifan, Tareq Saleh, Nisreen Abu Shahin, Maha ELBeltagy, Fatimah Obeidat, Duaa Qattan, Heba Kalbouneh, Noor A Barakat, Mohammad Alsalem
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
顺铂引起的认知障碍(化疗脑)影响相当大比例的癌症患者,并且没有既定的药物治疗方法。化学脑可能与神经炎症和氧化应激有关。褪黑激素是一种松果体激素,已知具有抗氧化、抗炎和神经保护潜力。在这项研究中,我们研究了顺铂引起的大鼠认知障碍以及褪黑激素是否可以改善或逆转这种障碍。行为测试包括在顺铂或顺铂 褪黑素治疗的条件下使用新型位置识别测试(NLRT)测量工作记忆,然后收集大鼠的大脑。随后用高尔基-考克斯染色法对大脑进行染色,然后检查各大脑的海马区CA3,并计算树突棘密度。顺铂治疗导致大鼠在 NLRT 中的表现出现缺陷(P < 0.05)。联合使用褪黑激素可预防这些缺陷(P < 0.05)。顺铂还降低了海马树突棘的密度(P < 0.0001),特别是CA3区域,而同时服用褪黑激素则显着逆转了这种降低(P < 0.001)。这项研究表明,褪黑激素可以改善顺铂引起的大鼠空间记忆缺陷和树突棘密度异常。鉴于褪黑激素是一种安全且广泛使用的补充剂,探索其在癌症治疗中作为姑息干预措施的用途是可行的。版权所有 © 2024 Wolters Kluwer Health, Inc. 保留所有权利。
Cisplatin-induced cognitive impairment (chemobrain) affects a considerable percentage of cancer patients and has no established pharmacological treatment. Chemobrain can be associated with neuroinflammation and oxidative stress. Melatonin, a pineal hormone, is known to have antioxidant, anti-inflammatory and neuroprotective potential. In this study, we investigated cisplatin-induced cognitive impairment in rats and whether melatonin can improve or reverse this impairment. Behavioral testing involved measuring working memory using the novel location recognition test (NLRT) under conditions of cisplatin or cisplatin + melatonin treatment, followed by the collection of rats' brains. The brains were subsequently stained with Golgi-Cox stain and then the hippocampus area CA3 of each one was examined, and dendritic spine density was calculated. Treatment with cisplatin resulted in deficits in the rats' performance in the NLRT (P < 0.05). These deficits were prevented by the coadministration of melatonin (P < 0.05). Cisplatin also reduced the density of dendritic spines in the hippocampus (P < 0.0001), specifically CA3 area, while the coadministration of melatonin significantly reversed this reduction (P < 0.001). This study showed that melatonin can ameliorate cisplatin-induced spatial memory deficits and dendritic spines density abnormalities in rats. Given that melatonin is a safe and wildly used supplement, it is feasible to explore its use as a palliative intervention in cancer treatment.Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.