Manganese exposure alters extracellular GABA, GABA receptor and transporter protein and mRNA levels in the developing rat brain.
Manganese exposure alters extracellular GABA, GABA receptor and transporter protein and mRNA levels in the developing rat brain.
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DOI：
10.1016/j.neuro.2008.08.002
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发表时间：
2008-11
期刊：
影响因子：
3.4
通讯作者：
Erikson KM
中科院分区：
文献类型：
--
作者：
Anderson JG;Fordahl SC;Cooney PT;Weaver TL;Colyer CL;Erikson KM
不像其他必需微量元素（例如，锌和铁），锰（Mn）的毒性在人群中比其缺乏症更常见。数据表明，多巴胺生物学的改变可能会驱动与锰神经毒性相关的效应，尽管最近γ-氨基丁酸（GABA）已被牵连。此外，缺铁（ID），一种常见的营养问题，可能会导致神经化学紊乱，促进锰在大脑中的积累。从我们的实验室以前的数据显示，脑组织水平的GABA以及减少3 H-GABA的摄取突触体作为锰暴露和ID的结果。这些结果表明，由于GABA转运和受体蛋白的表达改变，细胞外GABA的浓度可能增加。在这项研究中，将断奶雄性Sprague-Dawley大鼠随机分为四个饮食治疗组：对照组（CN; 35 mg Fe/kg饮食）、缺铁组（ID; 6 mg Fe/kg饮食）、CN + Mn补充组（通过饮用水; 1 g Mn/L）（CNMn）和ID + Mn补充组（IDMn）。使用在体内微透析，在纹状体中的细胞外GABA浓度的增加，观察到在响应锰暴露和ID，虽然相关性分析表明，细胞外GABA更多地与细胞外铁水平，而不是锰。通过Western印迹和RT-PCR分析，在检查的区域中观察到Mn暴露和ID的不同影响，对GAT-1，GABAA和GABAB的mRNA和蛋白质表达的影响在检查的区域之间和区域内不同。例如，锰暴露减少GAT-1蛋白表达约50%，在黑质，而增加mRNA表达约4倍，而在尾壳核mRNA表达下降，对蛋白表达没有影响。这些数据表明，锰暴露的结果在细胞外GABA浓度增加，通过改变运输和受体蛋白的表达，这可能是锰中毒的神经学特征的基础。
Unlike other essential trace elements (e.g., zinc and iron) it is the toxicity of manganese (Mn) that is more common in human populations than its deficiency. Data suggest alterations in dopamine biology may drive the effects associated with Mn neurotoxicity, though recently γ-aminobutyric acid (GABA) has been implicated. In addition, iron deficiency (ID), a common nutritional problem, may cause disturbances in neurochemistry by facilitating accumulation of Mn in the brain. Previous data from our lab have shown decreased brain tissue levels of GABA as well as decreased 3H-GABA uptake in synaptosomes as a result of Mn exposure and ID. These results indicate a possible increase in the concentration of extracellular GABA due to alterations in expression of GABA transport and receptor proteins. In this study weanling-male Sprague-Dawley rats were randomly placed into one of four dietary treatment groups: control (CN; 35 mg Fe/kg diet), iron-deficient (ID; 6 mg Fe/kg diet), CN with Mn supplementation (via the drinking water; 1 g Mn/L) (CNMn), and ID with Mn supplementation (IDMn). Using in vivo microdialysis, an increase in extracellular GABA concentrations in the striatum was observed in response to Mn exposure and ID although correlational analysis reveals that extracellular GABA is related more to extracellular iron levels and not Mn. A diverse effect of Mn exposure and ID was observed in the regions examined via Western blot and RT-PCR analysis, with effects on mRNA and protein expression of GAT-1, GABAA, and GABAB differing between and within the regions examined. For example, Mn exposure reduced GAT-1 protein expression by approximately 50% in the substantia nigra, while increasing mRNA expression approximately four-fold, while in the caudate putamen mRNA expression was decreased with no effect on protein expression. These data suggest that Mn exposure results in an increase in extracellular GABA concentrations via altered expression of transport and receptor proteins, which may be the basis of the neurological characteristics of manganism.
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影响因子：
3.8
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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作者：
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