Abstract

Copper (Cu) is a heavy metal with the ability to induce, at high levels, neurobehavioral alterations, and oxidative stress (OS). On the other hand, melatonin (Mel) is a neurohormone that protects neurons from OS and has a modulatory effect on several behavioral processes. The present experiment was aimed to examine the effect of Mel treatment on Cu-induced anxiety-like, depression-like behaviors, memory impairment, and OS in hippocampus. Herein, adult Wistar rats of both genders received daily Mel (4 mg/kg) thirty minutes before CuCl₂ (1 mg/kg), by intraperitoneal injections for 8 weeks. After the administration period, all rats were submitted to the behavioral tests. Thereafter, OS parameters and histology of the hippocampus were evaluated. The results demonstrate that Mel treatment attenuated Cu-induced anxiety-like and depression-like behaviors, and it improved memory deficits Cu-treated rats. Furthermore, Mel attenuated Cu-provoked OS by reducing lipid peroxidation (LPO) and nitric oxide (NO) levels and enhancing superoxide dismutase (SOD) and catalase (CAT) activities in the hippocampus. The histopathological analysis also supported these results. In conclusion, these findings show that Mel treatment exerted neuroprotective effects against Cu-induced neurobehavioral changes which may be related to reduction of hippocampal OS. Besides, the effects of Cu and Mel were gender dependent, being more marked in females compared to male rats.

摘要

铜 (Cu) 是一种重金属，能够在高水平上诱导神经行为改变和氧化应激 (OS)。另一方面，褪黑激素 (Mel) 是一种神经激素，可保护神经元免受 OS 影响，并对多种行为过程具有调节作用。本实验旨在检查 Mel 治疗对 Cu 诱导的海马焦虑样、抑郁样行为、记忆障碍和 OS 的影响。在此，两种性别的成年 Wistar 大鼠在 CuCl ₂ (1 mg/kg) 前 30 分钟通过腹膜内注射每天接受 Mel (4 mg/kg) 8  周。给药期结束后，对所有大鼠进行行为测试。此后，评估了海马的 OS 参数和组织学。结果表明，Mel 治疗减轻了铜诱导的焦虑样和抑郁样行为，并改善了铜治疗大鼠的记忆缺陷。此外，Mel 通过降低脂质过氧化 (LPO) 和一氧化氮 (NO) 水平以及增强海马中的超氧化物歧化酶 (SOD) 和过氧化氢酶 (CAT) 活性来减弱铜引发的 OS。组织病理学分析也支持这些结果。总之，这些发现表明，Mel 治疗对 Cu 诱导的神经行为变化具有神经保护作用，这可能与海马 OS 的降低有关。此外，Cu 和 Mel 的影响与性别有关，