Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA.
Ann Neurol. 2010 Jul;68(1):70-80. doi: 10.1002/ana.22018.
Exposure 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.
We now report that consumption of washed cycad flour pellets by Sprague-Dawley male rats induces progressive parkinsonism.
Cycad-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). alpha-Synuclein (alpha-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 alpha-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 alpha-syn aggregates in the SN.
Cycad-fed rats exhibit progressive behavioral, biochemical, and histological hallmarks of parkinsonism, coupled with a lack of fatality.
接触多种药物、化学物质或环境因素都可能导致帕金森病。流行病学证据支持关岛查莫罗人群食用由 Cycas micronesica 植物种子制成的面粉与肌萎缩侧索硬化/帕金森病痴呆复合征之间存在因果关系。
我们现在报告，Sprague-Dawley 雄性大鼠食用 Cycad 面粉球粒会引发进行性帕金森病。
食用 Cycad 的大鼠在喂食 2 至 3 个月后出现运动异常，如自发性单侧旋转、拖曳步态和刻板行为。从食用 Cycad 的大鼠大脑的组织学和生化检查中发现纹状体（STR）中多巴胺及其代谢物的水平最初降低，随后黑质致密部（SNc）中的多巴胺能（DAergic）细胞体发生神经退行性变。在 SNc 的 DAergic 神经元和 STR 的神经元纤维中发现了 alpha-突触核蛋白（alpha-syn；蛋白水解酶抗性）和泛素聚集体。此外，我们在蓝斑核和扣带皮质的神经元中鉴定出 alpha-syn 聚集体。在慢性食用 Cycad 面粉后，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中，Cycad 的有机提取物可导致多巴胺神经元选择性丧失和 SN 中的 alpha-syn 聚集体。
食用 Cycad 的大鼠表现出进行性行为、生化和组织学帕金森病特征，同时缺乏致命性。
