Mullin Elizabeth J, Wegst-Uhrich Stacia R, Ding Dalian, Manohar Senthilvelan, Krishnan Muthaiah Vijaya Prakash, Salvi Richard, Aga Diana S, Roth Jerome A
Department of Chemistry, University at Buffalo, Buffalo, NY, 14260, USA.
Department of Communicative Disorders and Sciences, University at Buffalo, Buffalo, NY, 14214, USA.
Biometals. 2015 Dec;28(6):1009-16. doi: 10.1007/s10534-015-9885-1. Epub 2015 Oct 3.
Manganese (Mn), iron (Fe), zinc (Zn), and copper (Cu) are essential transitions metals that are required in trace amounts, however chronic exposure to high concentrations can cause severe and irreversible neurotoxicity. Since prolonged exposure to Mn leads to manganism, a disorder exhibiting a diverse array of neurological impairments progressing to a debilitating and irreversible extrapyramidal condition symptomatically similar to Parkinson's disease, we measured the concentration of Mn as well as Fe, Zn and Cu in three region of the brain (globus pallidus, striatum and inferior colliculus) and three regions in the cochlea (stria vascularis, basilar membrane and modiolus) under normal conditions or after 30 or 60 days of oral administration of Mn (10 mg/ml ad libitum). Under normal conditions, Mn, Zn and Fe were typically higher in the cochlea than in the three brain regions whereas Cu was equal to or lower. Oral treatment with Mn for 30 or 60 days resulted in 20-75 % increases in Mn concentrations in both cochlea and brain samples, but had little effect on Cu and Fe levels. In contrast, Zn levels decreased (20-80 %) with Mn exposure. Our results show for the first time how prolonged oral Mn-ingestion affects the concentration of Mn, Cu, Zn and Fe, in the three regions of the cochlea, the inferior colliculus in auditory midbrain and the striatum and globus pallidus, two regions implicated in Parkinson's disorder. The Mn-induced changes in the concentration of Mn, Cu, Zn and Fe may provide new insights relevant to the neurotoxicity of Mn and the transport and accumulation of these metals in cochlea and brain.
锰(Mn)、铁(Fe)、锌(Zn)和铜(Cu)是必需的过渡金属,需求量极少,但长期接触高浓度这些金属会导致严重且不可逆的神经毒性。由于长期接触锰会导致锰中毒,这种疾病表现出一系列不同的神经损伤,逐渐发展为一种衰弱且不可逆的锥体外系病症,症状与帕金森病相似,因此我们测量了正常条件下或口服锰(10毫克/毫升,随意饮用)30天或60天后,大脑三个区域(苍白球、纹状体和下丘)以及耳蜗三个区域(血管纹、基底膜和蜗轴)中的锰以及铁、锌和铜的浓度。在正常条件下,耳蜗中的锰、锌和铁通常比大脑的三个区域高,而铜则相等或更低。口服锰30天或60天导致耳蜗和大脑样本中的锰浓度增加20 - 75%,但对铜和铁水平影响不大。相比之下,锌水平随着锰暴露而下降(20 - 80%)。我们的结果首次表明,长期口服锰摄入如何影响耳蜗的三个区域、听觉中脑的下丘以及与帕金森病相关的两个区域纹状体和苍白球中锰、铜、锌和铁的浓度。锰诱导的锰、铜、锌和铁浓度变化可能为锰的神经毒性以及这些金属在耳蜗和大脑中的运输和积累提供新的见解。