In vitro and whole animal evidence that methylmercury disrupts GABAergic systems in discrete brain regions in captive mink
In vitro and whole animal evidence that methylmercury disrupts GABAergic systems in discrete brain regions in captive mink
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DOI：
10.1016/j.cbpc.2010.01.001
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发表时间：
2010-04-01
影响因子：
3.9
通讯作者：
Chan, Laurie H. M.
中科院分区：
文献类型：
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作者：
Basu, Niladri;Scheuhammer, Anton M.;Chan, Laurie H. M.
使用体外和体内（整只动物）实验方法，在圈养的幼年雄性美国水貂 (Neovison vison) 的离散大脑区域中评估了汞 (Hg) 对 GABA 能系统关键成分的影响。对皮质脑组织的体外研究表明，无机汞（HgCl2：IC50 = 0.5 +/- 0.2 μM）和甲基汞（MeHgCl；IC50 = 1.6 +/- 0.2 μM）抑制谷氨酸脱羧酶（GAD；EC 4.1.1.15）活性。 [H-3]-蕈醇与 GABA(A) 受体的结合没有与汞相关的影响（IC50 > 100 μM）。 HgCl2 (IC50 = 0.8 +/- 0.3 mu M) 但 MeHgCl (IC50 > 100 mu M) 不会抑制 GABA 转氨酶 (GABA-T; EC 2.6.1.19) 活性。在一项整体动物研究中，每天喂食相关水平的 MeHgCl（0 至 2 mu g/g 饲料，ppm）的圈养水貂连续 89 天，测量其大脑区域（枕叶皮层、小脑、脑干和基底神经节）的 GABA 能功能的神经化学指标。未测量到对 GAD 活性的影响。在几个脑区发现 [H-3]-蝇蕈醇与 GABA(A) 受体的结合和 GABA-T 活性呈浓度依赖性降低，在脑干和基底神经节中测量到的降低幅度高达 94%（GABA(A) 受体水平）和 71%（GABA-T 活性）。这些结果表明，长期暴露于环境相关水平的甲基汞会破坏 GABA 信号传导。鉴于 GABA 是哺乳动物神经系统中主要的抑制性神经递质，其功能的长期破坏可能是甲基汞在相关水平对动物健康产生亚临床影响的基础。 (C) 2010 Elsevier Inc. 保留所有权利。
The effects of mercury (Hg) on key components of the GABAergic system were evaluated in discrete brain regions of captive juvenile male American mink (Neovison vison) using in vitro and in vivo (whole animal) experimental approaches. In vitro studies on cortical brain tissues revealed that inorganic Hg (HgCl2: IC50 = 0.5 +/- 0.2 mu M) and methyl Hg (MeHgCl; IC50 = 1.6 +/- 0.2 mu M) inhibited glutamic acid decarboxylase (GAD; EC 4.1.1.15) activity. There were no Hg-related effects on [H-3]-muscimol binding to GABA(A) receptors (IC50s > 100 mu M). HgCl2 (IC50 = 0.8 +/- 0.3 mu M) but not MeHgCl (IC50 > 100 mu M) inhibited GABA-transaminase (GABA-T; EC 2.6.1.19) activity. In a whole animal study, neurochemical indicators of GABAergic function were measured in brain regions (occipital cortex, cerebellum, brain stem, and basal ganglia) of captive mink fed relevant levels of MeHgCl (0 to 2 mu g/g feed, ppm) daily for 89 d. No effects on GAD activity were measured. Concentration-dependent decreases in [H-3]-muscimol binding to GABA(A) receptors and GABA-T activity were found in several brain regions, with reductions as great as 94% (for GABA(A) receptor levels) and 71% (for GABA-T activity) measured in the brain stem and basal ganglia. These results show that chronic exposure to environmentally relevant levels of MeHg disrupts GABAergic signaling. Given that GABA is the main inhibitory neurotransmitter in the mammalian nervous system, prolonged disruptions of its function may underlie the sub-clinical impacts of MeHg at relevant levels to animal health. (C) 2010 Elsevier Inc. All rights reserved.