The effects of manganese on glutamate, dopamine and γ-aminobutyric acid regulation
The effects of manganese on glutamate, dopamine and γ-aminobutyric acid regulation
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DOI：
10.1016/j.neuint.2005.10.012
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发表时间：
2006-05-01
影响因子：
4.2
通讯作者：
Aschner, M
中科院分区：
文献类型：
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作者：
Fitsanakis, VA;Au, C;Aschner, M
暴露于高水平的锰(Mn)会导致一种神经疾病，称为锰中毒，由于两者都涉及基底节回路，因此与帕金森病有相似的表型。最初的锰中毒症状可能是由于苍白球的参与，这是一个富含伽马-氨基丁酸(GABA)投射的区域，而帕金森病的最初症状与黑质的退化有关，黑质是一个多巴胺能核。此外，已知谷氨酸调节受到大脑中锰水平增加的影响。由于锰主要聚集在基底节，它可能会影响所有三种神经递质的调节和相互作用。这篇综述将集中于这些神经递质在基底节内的回路，并讨论锰暴露与这些神经递质水平变化之间的潜在部位以及时间关系。虽然大多数研究都集中在多巴胺能系统的干扰上，但有证据表明，锰中毒的早期后果也包括GABA调节的干扰以及与谷氨酸能相关的兴奋性毒性。最后，我们建议目前的研究集中在这些基础神经节神经化学物质的相互依赖上，更多地强调GABA能和谷氨酸能系统。(C)2006爱思唯尔有限公司。保留所有权利。
Exposure to high levels of manganese (Mn) results in a neurological disorder, termed manganism, which shares a similar phenotype to Parkinson's disease due to the involvement of the basal ganglia circuitry in both. The initial symptoms of manganism are likely due to the involvement of the globus pallidus, a region rich gamma-aminobutyric acid (GABA) projections, while those of Parkinson's disease are related to the degeneration of the substantia nigra, a dopaminergic nucleus. Additionally, it is known that glutamate regulation is affected by increases in brain Mn levels. As Mn predominantly accumulates in the basal ganglia, it potentially could affect the regulation and interactions of all three neurotransmitters. This review will focus on the circuitry of these neurotransmitters within the basal ganglia and address potential sites for, as well as the temporal relationship, between Mn exposure and changes in the levels of these neurotransmitters. While most research has focused on perturbations in the dopaminergic system, there is evidence to support that early consequences of manganism, also include disturbances in GABA regulation as well as glutarnatergic-related excitotoxicity. Finally, we suggest that current research focus on the interdependence of these basal ganglial neurochemicals, with a greater emphasis on the GABAergic and glutamatergic systems. (C) 2006 Elsevier Ltd. All rights reserved.