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首页> 外文期刊>Annals of Neurology >Environmental neurotoxin-induced progressive model of parkinsonism in rats
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Environmental neurotoxin-induced progressive model of parkinsonism in rats

机译:环境神经毒素诱导的大鼠帕金森病进展模型

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ObjectiveExposure to a number of drugs, chemicals, or environmental factors can cause parkinsonism. Epidemiologic evidence supports a causal link between the consumption of flour made from the washed seeds of the plant Cycas micronesica by the Chamorro population of Guam and the development of amyotrophic lateral sclerosis/parkinsonism dementia complex.MethodsWe now report that consumption of washed cycad flour pellets by Sprague-Dawley male rats induces progressive parkinsonism.ResultsCycad-fed rats displayed motor abnormalities after 2 to 3 months of feeding such as spontaneous unilateral rotation, shuffling gait, and stereotypy. Histological and biochemical examination of brains from cycad-fed rats revealed an initial decrease in the levels of dopamine and its metabolites in the striatum (STR), followed by neurodegeneration of dopaminergic (DAergic) cell bodies in the substantia nigra (SN) pars compacta (SNc). -Synuclein (-syn; proteinase K-resistant) and ubiquitin aggregates were found in the DAergic neurons of the SNc and neurites in the STR. In addition, we identified -syn aggregates in neurons of the locus coeruleus and cingulate cortex. No loss of motor neurons in the spinal cord was found after chronic consumption of cycad flour. In an organotypic slice culture of the rat SN and the striatum, an organic extract of cycad causes a selective loss of dopamine neurons and -syn aggregates in the SN.InterpretationCycad-fed rats exhibit progressive behavioral, biochemical, and histological hallmarks of parkinsonism, coupled with a lack of fatality. ANN NEUROL 2010;68:70–80
机译:目的接触多种药物,化学物质或环境因素会导致帕金森氏症。流行病学证据支持关岛Chamorro种群食用由密苏里州植物Cycas micronesica洗净的种子制成的面粉与肌萎缩性侧索硬化/帕金森氏痴呆综合症的发展之间存在因果关系。 Sprague-Dawley雄性大鼠诱发进行性帕金森氏病。结果,用Cycad喂养的大鼠在进食2至3个月后表现出运动异常,例如自发单侧旋转,步态改组和定型。对苏铁喂养的大鼠大脑的组织学和生化检查显示,纹状体(STR)中多巴胺及其代谢物的含量最初有所下降,随后黑质(SN)pars compacta(SN)中多巴胺能(DAergic)细胞体发生神经退行性变( SNc)。在SNc的DA能神经元和STR的神经突中发现了突触核蛋白(-syn;对蛋白酶K有抗性)和泛素聚集体。另外,我们在蓝斑和扣带回皮层的神经元中鉴定了-syn聚集体。长期食用苏铁粉后未发现脊髓运动神经元丢失。在大鼠SN和纹状体的器官型切片培养物中,苏铁的有机提取物导致SN中的多巴胺神经元和-syn聚集体选择性丢失。解释用Cycad喂养的大鼠表现出帕金森综合征的行为,生化和组织学特征没有死亡。 ANN NEUROL 2010; 68:70–80

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