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孕期长期低剂量暴露于甲基汞会损害成年C57/B6小鼠的运动和记忆功能。

Chronic, low-dose prenatal exposure to methylmercury impairs motor and mnemonic function in adult C57/B6 mice.

作者信息

Montgomery Karienn S, Mackey Jessica, Thuett Kerry, Ginestra Stephanie, Bizon Jennifer L, Abbott Louise C

机构信息

Department of Psychology, Texas A&M University, College Station, TX 77843-4235, USA.

出版信息

Behav Brain Res. 2008 Aug 5;191(1):55-61. doi: 10.1016/j.bbr.2008.03.008. Epub 2008 Mar 16.

Abstract

Methylmercury (MeHg) has cytotoxic effects on animals and humans, and a major target organ for MeHg is the central nervous system (CNS). It is well known that the developing CNS is extremely vulnerable to MeHg-induced changes in comparison to the mature brain. Most studies have concentrated on the direct effects of high levels of prenatal MeHg exposure. Surprisingly, behavioral outcomes found in adult offspring exposed developmentally to the neurotoxic effects of chronic, low-dose mercury more akin to ingestion in humans are not well characterized. The objective of this study was to determine whether such exposure produces deleterious effects on behavior in adult mice, including motor/coordination abilities, overall activity and mnemonic function. Developing mouse fetuses were exposed in utero during gestational days 8-18 by giving pregnant C57Bl/6J female mice food containing MeHg at a daily dose of 0.01 mg/kg body weight. Adult mice prenatally exposed to MeHg exhibited significant deficits in motor abilities, coordination, and overall activity, as measured by rotarod, footprint analysis and open field. In addition, MeHg-exposed mice were impaired with respect to reference memory but not in a visible, cued version of the Morris water maze task. These results indicate that prenatal exposure to the lowest dose of MeHg examined to date can have long-lasting motor and cognitive consequences on adult offspring. These findings have far reaching implications related to putative safe levels of MeHg ingestion, particularly during pregnancy, and increasing rates of cognitive and psychological disorders (e.g. attention hyperactivity deficit disorder, autism) in our society.

摘要

甲基汞(MeHg)对动物和人类具有细胞毒性作用,而MeHg的一个主要靶器官是中枢神经系统(CNS)。众所周知,与成熟大脑相比,发育中的中枢神经系统极易受到MeHg诱导的变化影响。大多数研究都集中在产前高水平MeHg暴露的直接影响上。令人惊讶的是,成年后代在发育过程中暴露于慢性低剂量汞的神经毒性作用(更类似于人类摄入情况)所产生的行为结果尚未得到充分描述。本研究的目的是确定这种暴露是否会对成年小鼠的行为产生有害影响,包括运动/协调能力、整体活动和记忆功能。在妊娠第8至18天,通过给怀孕的C57Bl/6J雌性小鼠喂食含MeHg的食物(每日剂量为0.01 mg/kg体重),使发育中的小鼠胎儿在子宫内暴露。通过转棒试验、足迹分析和旷场试验测量,产前暴露于MeHg的成年小鼠在运动能力、协调性和整体活动方面表现出明显缺陷。此外,暴露于MeHg的小鼠在参考记忆方面受损,但在莫里斯水迷宫任务的可见、线索版本中未受损。这些结果表明,产前暴露于迄今为止所检测到的最低剂量的MeHg,可能会对成年后代产生长期的运动和认知后果。这些发现对于MeHg摄入的假定安全水平具有深远影响,特别是在怀孕期间,以及在我们社会中认知和心理障碍(如注意力缺陷多动障碍、自闭症)发病率不断上升的情况下。

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