Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI, USA.
Comp Biochem Physiol C Toxicol Pharmacol. 2010 Apr;151(3):379-85. doi: 10.1016/j.cbpc.2010.01.001. Epub 2010 Jan 7.
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 (HgCl(2); IC50=0.5+/-0.2microM) and methyl Hg (MeHgCl; IC50=1.6+/-0.2microM) inhibited glutamic acid decarboxylase (GAD; EC 4.1.1.15) activity. There were no Hg-related effects on [(3)H]-muscimol binding to GABA(A) receptors (IC50s>100microM). HgCl(2) (IC50=0.8+/-0.3microM) but not MeHgCl (IC50>100microM) 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 2microg/g feed, ppm) daily for 89d. No effects on GAD activity were measured. Concentration-dependent decreases in [(3)H]-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.
采用离体和整体动物实验方法，评估了汞（Hg）对圈养雄性美洲水貂（Neovison vison）大脑特定区域γ-氨基丁酸能系统关键成分的影响。皮质脑组织的离体研究表明，无机汞（HgCl2；IC50=0.5+/-0.2μM）和甲基汞（MeHgCl；IC50=1.6+/-0.2μM）抑制谷氨酸脱羧酶（GAD；EC 4.1.1.15）活性。Hg 对[3H]-muscimol 与 GABA（A）受体结合没有相关影响（IC50s>100μM）。HgCl2（IC50=0.8+/-0.3μM）而非 MeHgCl（IC50>100μM）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，在圈养水貂（每天喂食相关剂量的 MeHgCl（0 至 2μg/g 饲料，ppm），共 89 天）的大脑区域（枕叶皮质、小脑、脑干和基底神经节）中测量了 GABA 能功能的神经化学指标。未测量到 GAD 活性的变化。在几个脑区发现[3H]-muscimol 与 GABA（A）受体结合和 GABA-T 活性呈浓度依赖性降低，在脑干和基底神经节中，GABA（A）受体水平降低高达 94%，GABA-T 活性降低高达 71%。这些结果表明，慢性暴露于环境相关水平的 MeHg 会破坏 GABA 能信号传递。鉴于 GABA 是哺乳动物神经系统中的主要抑制性神经递质，其功能的长期破坏可能是 MeHg 在相关水平对动物健康产生亚临床影响的基础。
