Vehovszky Agnes, Szabó Henriette, Hiripi László, Elliott Christopher J H, Hernádi László
Balaton Limnological Research Institute, Hungarian Academy of Sciences, Department of Experimental Zoology, Tihany, PO Box 35, Hungary H-8237.
Eur J Neurosci. 2007 Apr;25(7):2123-30. doi: 10.1111/j.1460-9568.2007.05467.x.
Parkinson's disease is a neurodegenerative disorder, related to the loss of dopamine (DA)-containing neurons in the substantia nigra. In experimental animals, both vertebrates and invertebrates, rotenone, a commercially available organic pesticide, induces symptoms of Parkinson's disease. We found that that rotenone is toxic to the pond snail Lymnaea stagnalis (4-day LC50 0.8 microM). Rotenone, at concentrations from 0.1 to 5 microM, caused progressive and irreversible behavioural deficits in both acute and chronic exposure. Chronic exposure to 0.5 microM rotenone led to a progressive decrease in spontaneous locomotion and in feeding, reaching almost 100% inhibition of both behaviours by the 7th day of rotenone treatment. In the central nervous system preparation made on the 7th day of treatment the postsynaptic potentials evoked by the identified dopaminergic RPeD1 neuron disappeared whereas the synaptic inputs received by the RPeD1 from a peptidergic neuron (VD4) were still functional. Immunostaining revealed that the tyrosine hydroxylase immunoreactivity decreased below the detectable level in both the RPeD1 cell body and its axonal processes. Finally, HPLC assay showed a significant (25%) decrease in DA level in the CNS by the 7th day of rotenone treatment. We conclude that, as in vertebrates, rotenone disrupts feeding and locomotion of the model mollusc Lymnaea stagnalis. One possible target of rotenone is the dopaminergic neurons in the CNS. We therefore suggest that Lymnaea stagnalis is a suitable invertebrate model for the study of Parkinson's disease, allowing direct analysis of the response of dopaminergic systems to rotenone at behavioural, cellular and neuronal levels.
帕金森病是一种神经退行性疾病，与黑质中含多巴胺（DA）的神经元丧失有关。在实验动物中，包括脊椎动物和无脊椎动物，鱼藤酮这种市售的有机农药会诱发帕金森病症状。我们发现鱼藤酮对椎实螺有毒（4天半数致死浓度为0.8微摩尔）。鱼藤酮浓度在0.1至5微摩尔时，无论是急性暴露还是慢性暴露，都会导致渐进性且不可逆的行为缺陷。慢性暴露于0.5微摩尔鱼藤酮会导致自发运动和摄食逐渐减少，在鱼藤酮处理的第7天，这两种行为几乎被完全抑制。在处理第7天制备的中枢神经系统标本中，已鉴定的多巴胺能RPeD1神经元诱发的突触后电位消失，而RPeD1从肽能神经元（VD4）接收的突触输入仍有功能。免疫染色显示，酪氨酸羟化酶免疫反应性在RPeD1细胞体及其轴突过程中均降至可检测水平以下。最后，高效液相色谱分析显示，在鱼藤酮处理的第7天，中枢神经系统中的多巴胺水平显著下降（25%）。我们得出结论，与脊椎动物一样，鱼藤酮会扰乱模式软体动物椎实螺的摄食和运动。鱼藤酮的一个可能靶点是中枢神经系统中的多巴胺能神经元。因此，我们认为椎实螺是研究帕金森病的合适无脊椎动物模型，可在行为、细胞和神经元水平上直接分析多巴胺能系统对鱼藤酮的反应。
