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母体饮食中摄入甲基汞和二十二碳六烯酸对仔鼠脑基因表达和神经行为反应的影响

Cerebral gene expression and neurobehavioural responses in mice pups exposed to methylmercury and docosahexaenoic acid through the maternal diet.

机构信息

National Institute of Nutrition and Seafood Research (NIFES), Post Box 2029 Nordnes 5817 Bergen, Norway.

出版信息

Environ Toxicol Pharmacol. 2012 Jan;33(1):26-38. doi: 10.1016/j.etap.2011.10.001. Epub 2011 Oct 13.

DOI:10.1016/j.etap.2011.10.001
PMID:22056564
Abstract

Methylmercury (MeHg) is an environmental neurotoxicant with adverse effects particularly noted in the developing brain. The main source of MeHg exposure is seafood. However, fish is also an important source of n-3 fatty acids such as docosahexaenoic acid (DHA) which has neuroprotective effects, and which plays an important role during the prenatal development of the central nervous system. The aim of the present study was to examine the effects of DHA and MeHg individually, and in combination, on development using accumulation, behavioural and transcriptomic endpoints in a mammalian model. Analyses were performed on 15 day old mice which had been exposed to varying levels of DHA (8 or 24 mg/kg) and/or MeHg (4 mg/kg) throughout development via the maternal diet. Supplementation of the maternal diet with DHA reduced MeHg accumulation in the brain. An accelerated development of grasping reflex was seen in mice offspring in the 'MeHg+high DHA' group when compared to 'MeHg' and 'control'. Exposure to MeHg and DHA had an impact on cerebral gene expression as assessed by microarray and qPCR analysis. The results from the present study show the potential of DHA for alleviating toxicity caused by MeHg. This information may contribute towards refining risk/benefit assessment of seafood consumption and may enhance understanding of discrepancies between epidemiological studies of MeHg neurodevelopmental toxicity.

摘要

甲基汞(MeHg)是一种环境神经毒素,对发育中的大脑有不良影响。MeHg 暴露的主要来源是海鲜。然而,鱼类也是 n-3 脂肪酸(如二十二碳六烯酸(DHA))的重要来源,这些脂肪酸具有神经保护作用,并在中枢神经系统的产前发育中发挥重要作用。本研究的目的是使用哺乳动物模型,通过积累、行为和转录组终点,单独和联合研究 DHA 和 MeHg 对发育的影响。对 15 天大的幼鼠进行了分析,这些幼鼠在整个发育过程中通过母体饮食暴露于不同水平的 DHA(8 或 24 mg/kg)和/或 MeHg(4 mg/kg)。母体饮食中补充 DHA 可减少脑中 MeHg 的积累。与“MeHg”和“对照”相比,“MeHg+高 DHA”组的幼鼠抓握反射发育加快。通过微阵列和 qPCR 分析评估,MeHg 和 DHA 的暴露对大脑基因表达有影响。本研究的结果表明,DHA 有缓解 MeHg 毒性的潜力。这些信息可能有助于完善对海鲜消费的风险/效益评估,并增强对流行病学研究中 MeHg 神经发育毒性差异的理解。

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