Boudreau Heather S, Krol Karmen M, Eibl Joseph K, Williams Linda D, Rossiter John P, Palace Vincent P, Ross Gregory M
Department of Physiology, Queen's University, Kingston, ON, Canada.
Aquat Toxicol. 2009 May 17;92(4):258-63. doi: 10.1016/j.aquatox.2009.02.011. Epub 2009 Feb 27.
Alpha-synuclein protein aggregates are a major component of Lewy bodies, the intracytoplasmic inclusions found in dopaminergic neurons that are a defining characteristic of Parkinson's disease. Other "synucleopathies" include dementia with Lewy bodies and multisystem atrophy. In vitro, the formation of these deposits can be induced by a number of substances, including metal ions. Fish provide a useful model to study the long-term biological effects of metal ion exposure, but to date no studies have been reported concerning such exposures with respect to alpha-synuclein aggregation. Mature white sucker fish (Catostomus commersoni; aged 5-8 years) were sampled from two sites within the Red Lake area of Northwestern Ontario, a region highly contaminated by metal ions due to mining activity. Individual fish were characterized with respect to liver metal ion uptake and metallothionein levels. Central nervous system (CNS) tissues of fish from test sites representing high and low metal ion contamination were examined immunohistochemically using a polyclonal antibody recognising alpha-synuclein protein. We demonstrate here that the CNS of fish exposed to elevated metal ion environments had increased alpha-synuclein-like immunoreactive aggregates, potentially reflecting metal ion exposure leading to CNS toxicity. These findings demonstrate that fish may be an important new model for studying environmental risk factors and the pathology associated with Parkinson's disease.
α-突触核蛋白聚集体是路易小体的主要成分，路易小体是在多巴胺能神经元中发现的胞质内包涵体，是帕金森病的一个决定性特征。其他“突触核蛋白病”包括路易体痴呆和多系统萎缩。在体外，这些沉积物的形成可由多种物质诱导，包括金属离子。鱼类为研究金属离子暴露的长期生物学效应提供了一个有用的模型，但迄今为止，尚未有关于此类暴露与α-突触核蛋白聚集相关的研究报道。成熟的白吸盘鱼（Catostomus commersoni；年龄5 - 8岁）取自安大略省西北部红湖地区的两个地点，该地区因采矿活动而受到金属离子的高度污染。对每条鱼的肝脏金属离子摄取和金属硫蛋白水平进行了测定。使用识别α-突触核蛋白的多克隆抗体，对来自代表高金属离子污染和低金属离子污染测试地点的鱼类中枢神经系统（CNS）组织进行免疫组织化学检查。我们在此证明，暴露于高金属离子环境的鱼类中枢神经系统中，α-突触核蛋白样免疫反应性聚集体增加，这可能反映了金属离子暴露导致中枢神经系统毒性。这些发现表明，鱼类可能是研究环境风险因素以及与帕金森病相关病理学的一个重要新模型。
