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乙醇和甲基汞对发育中的中枢神经系统的干扰。

Interference of ethanol and methylmercury in the developing central nervous system.

作者信息

Maia Cristiane do Socorro Ferraz, Lucena Greice Maria Rodrigues de Souza, Corrêa Pollyanna Barbosa Farias, Serra Raphael Borges, Matos Robson Willian de Melo, Menezes Flávia da Cunha, Santos Setsuko Noro dos, Sousa João Batista de, Costa Edmar Tavares da, Ferreira Vania Maria Moraes

机构信息

Faculdade de Ciências da Saúde, Curso de Ciências Farmacêuticas, Universidade de Brasília, Distrito Federal 70910-900, Brazil.

出版信息

Neurotoxicology. 2009 Jan;30(1):23-30. doi: 10.1016/j.neuro.2008.11.008. Epub 2008 Nov 28.

DOI:10.1016/j.neuro.2008.11.008
PMID:19100288
Abstract

Studies involving alcohol and its interactions with other neurotoxicants represent the focus of several works of research due to the fact that the use of alcohol can sometimes leads to serious health problems. Fetal exposure to alcohol and mercury has a high incidence in some regions of Brazil, where there are pregnant women who are alcoholics and live in mining areas. This work was conducted to examine the effects of combined exposure to ethanol (EtOH) and methylmercury (MeHg) in rats during the development of the central nervous system (CNS). Experimental behavioral animal models/tests were used in order to examine locomotion, anxiety, depression and memory. Pregnant rats received tap water or EtOH 22.5% w/v (6.5 g/kg per day), by gavage) during pregnancy and breast-feeding. On the 15th day of pregnancy, some groups received 8 mg/kg of MeHg (by gavage). The groups were as follows: control, EtOH, MeHg and EtOH+MeHg. The experimental results showed that the EtOH, MeHg and EtOH+MeHg groups reduced the percentage of frequency and time spent in the open arms entries of the elevated plus-maze (EPM) test, when compared to the control group. This result suggests an anxiogenic behavioral response. The MeHg group increased locomotor activity in the arena and the immobility time in the forced swimming test, suggestive of depression-like behavior. The EtOH+MeHg group showed greater reductions in the percentages of frequency and time spent in the open arms entries in the EPM test, suggesting a sedative-behavior since the frequency of enclosed arm entries was affected. In the inhibitory avoidance task, the EtOH+MeHg group reduced the latency of the step-down response onto the grid floor, suggesting a cognitive and behavior dysfunctions. Taken together, the results suggest that EtOH and/or MeHg intoxication during the developing CNS may be a risk for deficits related to locomotor impairment, anxiety, depression and neurocognitive functions. There is a possibility that EtOH may prevent some of the MeHg responses, but the precise mechanism of action involved in this process needs to be considered for future research.

摘要

由于酒精的使用有时会导致严重的健康问题,涉及酒精及其与其他神经毒素相互作用的研究成为了几项研究工作的重点。在巴西的一些地区,胎儿接触酒精和汞的情况很常见,那里有酗酒的孕妇且居住在矿区。本研究旨在探讨大鼠在中枢神经系统(CNS)发育过程中联合暴露于乙醇(EtOH)和甲基汞(MeHg)的影响。使用实验性行为动物模型/测试来检测运动能力、焦虑、抑郁和记忆。怀孕大鼠在怀孕和哺乳期通过灌胃接受自来水或22.5% w/v的EtOH(6.5 g/kg/天)。在怀孕第15天,一些组接受8 mg/kg的MeHg(通过灌胃)。分组如下:对照组、EtOH组、MeHg组和EtOH+MeHg组。实验结果表明,与对照组相比,EtOH组、MeHg组和EtOH+MeHg组在高架十字迷宫(EPM)测试中进入开放臂的频率百分比和时间百分比降低。这一结果表明存在焦虑行为反应。MeHg组在竞技场中的运动活动增加,在强迫游泳测试中的不动时间增加,提示有类似抑郁的行为。EtOH+MeHg组在EPM测试中进入开放臂的频率百分比和时间百分比降低幅度更大,由于进入封闭臂的频率受到影响,提示有镇静行为。在抑制性回避任务中,EtOH+MeHg组降低了踏上网格地板的跳下反应潜伏期,提示存在认知和行为功能障碍。综合来看,结果表明在中枢神经系统发育过程中EtOH和/或MeHg中毒可能是导致运动障碍、焦虑、抑郁和神经认知功能缺陷的风险因素。EtOH有可能会阻止一些MeHg的反应,但这一过程中涉及的精确作用机制需要在未来的研究中加以考虑。

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