Amaro-Leal Ângela, Afonso Ana I, Machado Filipa, Shvachiy Liana, Rocha Isabel, Outeiro Tiago F, Geraldes Vera
Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health & Science, 2829-511 Almada, Portugal.
Faculdade de Medicina, Universidade de Lisboa, Av. Prof Egas Moniz, 1649-028 Lisbon, Portugal.
Biology (Basel). 2024 Nov 16;13(11):939. doi: 10.3390/biology13110939.
Cognitive impairment and anxiety are common side effects of chemotherapy, particularly with the use of doxorubicin (DOX), known as "chemobrain". This study aimed to examine the dose-dependent effects of DOX on cognitive decline, anxiety, and locomotor activity in healthy female Wistar rats. The rats were divided into groups receiving low (2 mg/kg), intermediate (4 mg/kg), and high (5 mg/kg) doses of DOX for four weeks, alongside a control group. Behavioral tests, including open field, elevated plus maze, and Y-maze tests, assessed anxiety, locomotion, and cognitive performance, while brain tissue analysis evaluated neuroinflammation using markers such as GFAP and Iba-1. The results showed that all doses of DOX induced anxiety-like behavior, reduced locomotion, and caused neuroinflammation in the hippocampus, with more severe effects at higher doses. Notably, high-dose DOX also caused short-term memory deficits. These findings highlight the dose-dependent nature of DOX's impact on behavior and cognition, suggesting that DOX plays a key role in the development of cognitive symptoms during chemotherapy. Further research is needed to understand the mechanisms behind these effects and to explore potential interventions.
认知障碍和焦虑是化疗常见的副作用，尤其是使用被称为“化疗脑”的阿霉素（DOX）时。本研究旨在检测DOX对健康雌性Wistar大鼠认知衰退、焦虑和运动活动的剂量依赖性影响。大鼠被分为接受低剂量（2毫克/千克）、中等剂量（4毫克/千克）和高剂量（5毫克/千克）DOX的组，持续四周，同时设置一个对照组。行为测试，包括旷场试验、高架十字迷宫试验和Y迷宫试验，评估焦虑、运动和认知表现，而脑组织分析使用诸如GFAP和Iba-1等标志物评估神经炎症。结果显示，所有剂量的DOX均诱发了焦虑样行为，降低了运动能力，并导致海马体神经炎症，高剂量时影响更严重。值得注意的是，高剂量DOX还导致短期记忆缺陷。这些发现突出了DOX对行为和认知影响的剂量依赖性，表明DOX在化疗期间认知症状的发展中起关键作用。需要进一步研究以了解这些影响背后的机制并探索潜在干预措施。
