A chemical neurotoxin, MPTP induces Parkinson's disease like phenotype, movement disorders and persistent loss of dopamine neurons in medaka fish

A chemical neurotoxin, MPTP induces Parkinson's disease like phenotype, movement disorders and persistent loss of dopamine neurons in medaka fish
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DOI:
10.1016/j.neures.2009.07.010
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发表时间:
2009-11-01
影响因子:
2.9
通讯作者:
Takahashi, Ryosuke
Takahashi, Ryosuke
中科院分区:
医学4区
文献类型:
--
作者:
Matsui, Hideaki;Taniguchi, Yoshihito;Takahashi, Ryosuke

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帕金森病(Parkinson's disease,PD)是第二常见的神经退行性疾病,与黑质中多巴胺能神经元的变性相关。为了建立一种新的PD模型,我们使用青鳉(Oryzias latipes)。用于遗传学和环境生物学的小型硬骨鱼。我们确定了酪氨酸羟化酶(TH)免疫阳性多巴胺能和去甲肾上腺素能纤维和神经元青鳉脑。建立了青鳉多巴胺能神经元的计数方法和青鳉行为的评价方法。我们将青鳉暴露于1-甲基-4-苯基-1,2,3,4-四氢吡啶(MPTP)。青鳉幼虫期处理,成虫期不处理。减少间脑中多巴胺能细胞的数量并减少自发运动,这让人想起人类PD患者和其他MPTP诱导的动物PD模型。在青鳉脑中的TH+神经元中,只有中间间脑室旁区的特定簇容易受到MPTP毒性的影响。对青鳉幼鱼经MPTP处理后,其多巴胺能细胞的数量在成体期并没有完全恢复。在这些MPTP处理的鱼的脑中持续降低的多巴胺量对于模拟人PD是有价值的。(C)2009年爱思唯尔爱尔兰有限公司和日本神经科学学会。All rights reserved.
Parkinson's disease (PD) is the second most common neurodegenerative disease associated with the degeneration of dopaminergic neurons in the substantia nigra. To create a new model of PD, we used medaka (Oryzias latipes). a small teleost that has been used in genetics and environmental biology. We identified tyrosine hydroxylase (TH) immunopositive dopaminergic and noradrenergic fibers and neurons in the medaka brain. Following establishment of a method for counting the number of dopaminergic neurons and an assay for the evaluation of the medaka behavior. we exposed medaka to 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP). The treatment of medaka at the larval stage, but not at adult stage. decreased the number of dopaminergic cells in the diencephalon and reduced spontaneous movement, which is reminiscent of human PD patients and other MPTP-induced animal PD models. Among TH+ neurons in the medaka brain, only a specific cluster in the paraventricular area of the middle diencephalon was vulnerable to MPTP toxicity. Detailed examinations of medaka transiently exposed to MPTP at the larval stage revealed that the number of dopaminergic cells was not fully recovered at their adult stage Moreover. the amounts of dopamine persistently decreased in the brain of these MPTP-treated fish MPTP-treated medaka is valuable for modeling human PD. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.