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长期铜暴露会导致雄性和雌性大鼠海马体氧化应激以及学习和记忆受损。

Chronic copper exposure leads to hippocampus oxidative stress and impaired learning and memory in male and female rats.

作者信息

Lamtai Mouloud, Zghari Oussama, Ouakki Sihame, Marmouzi Ilias, Mesfioui Abdelhalem, El Hessni Aboubaker, Ouichou Ali

机构信息

Laboratory of Genetics, Neuroendocrinology and Biotechnology, Faculty of Science, Ibn Tofail University, BP 133, Kénitra, 14000 Morocco.

Laboratoire de Pharmacologie et Toxicologie, équipe de Pharmacocinétique, Faculté de Médicine et Pharmacie, University Mohammed V in Rabat, Rabat Instituts, Rabat, Morocco.

出版信息

Toxicol Res. 2020 Mar 13;36(4):359-366. doi: 10.1007/s43188-020-00043-4. eCollection 2020 Oct.

Abstract

Environmental and occupational exposures to copper (Cu) play a pivotal role in the etiology of some neurological diseases and reduced cognitive functions. However, the precise mechanisms of its effects on cognitive function have not been yet thoroughly established. In our study, we aimed to investigate the behavior and neurochemical alterations in hippocampus of male and female rats, chronically exposed to copper chloride (CuCl) and the possible involvement of oxidative stress. Twenty-four rats, for each gender, were divided into control and three test groups (n = 6), and were injected intraperitoneally with saline (0.9% NaCl) or CuCl (0.25 mg/kg, 0.5 mg/kg and 1 mg/kg) for 8 weeks. After the treatment period, Y-maze test was used for the evaluation of spatial working memory and the Morris Water Maze (MWM) to test the spatial learning and memory. Biochemical determination of oxidative stress levels in hippocampus was performed. The main results of the present work are working memory impairment in spatial Y-maze which induced by higher Cu intake (1 mg/kg) in male and female rats. Also, In the MWM test, the spatial learning and memory were significantly impaired in rats treated with Cu at dose of 1 mg/kg. Additionally, markers of oxidative stress such as catalase, superoxide dismutase, lipid peroxidation products and nitric oxide levels were significantly altered following Cu treatments. These data propose that compromised behavior following Cu exposure is associated with increase in oxidative stress.

摘要

环境和职业性接触铜(Cu)在某些神经疾病的病因以及认知功能减退中起着关键作用。然而,其对认知功能影响的精确机制尚未完全明确。在我们的研究中,我们旨在调查长期暴露于氯化铜(CuCl)的雄性和雌性大鼠海马体中的行为和神经化学变化,以及氧化应激可能参与的情况。将每种性别的24只大鼠分为对照组和三个试验组(n = 6),并腹腔注射生理盐水(0.9% NaCl)或CuCl(0.25 mg/kg、0. mg/kg和1 mg/kg),持续8周。治疗期结束后,采用Y迷宫试验评估空间工作记忆,采用莫里斯水迷宫(MWM)测试空间学习和记忆。对海马体中的氧化应激水平进行生化测定。本研究的主要结果是,高铜摄入量(1 mg/kg)导致雄性和雌性大鼠在空间Y迷宫中出现工作记忆损伤。此外,在MWM试验中,用1 mg/kg剂量的铜处理的大鼠空间学习和记忆明显受损。此外,铜处理后,过氧化氢酶、超氧化物歧化酶、脂质过氧化产物和一氧化氮水平等氧化应激标志物发生了显著变化。这些数据表明,铜暴露后行为受损与氧化应激增加有关。

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