MPTP and MPP plus target specific aminergic cell populations in larval zebrafish
MPTP and MPP plus target specific aminergic cell populations in larval zebrafish
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DOI：
10.1111/j.1471-4159.2008.05793.x
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发表时间：
2009-02-01
影响因子：
4.7
通讯作者：
Panula, P.
中科院分区：
文献类型：
--
作者：
Sallinen, V. .;Torkko, V. .;Panula, P.
斑马鱼幼鱼提供了一个很好的模型来接近大脑疾病的机制，因为它们小大脑的结构异常可以与可量化的行为相关联。在这项研究中，1-甲基-4-苯基吡啶鎓（MPP+），一种在人类中诱导帕金森病的毒素，诱导间脑多巴胺能核的结构改变，以及在1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP），前毒素后，在几个神经元群中发现的结构改变，与游泳速度下降有关。多巴胺能组的详细细胞计数表明MPTP后酪氨酸羟化酶表达神经元的瞬时下降高达约50%。MPTP效应对单胺氧化酶抑制剂丙炔苯丙胺部分敏感。对发育中的儿茶酚胺能细胞群的详细分析表明，细胞群出现在其最终位置，并且未观察到从原始位置的明显显著迁移。一个5-HT神经元组也受到MPTP处理的影响，而其他组保持完整，这表明该作用是选择性的。新的命名为发展中的儿茶酚胺能细胞群相应的成人组介绍。由第5、6和11组组成的间脑细胞群对MPTP和MPP+均敏感，在这方面类似于哺乳动物黑质。结果表明，MPTP和MPP+诱导斑马鱼幼鱼短暂的功能缺陷和运动障碍。
Larval zebrafish offers a good model to approach brain disease mechanisms, as structural abnormalities of their small brains can be correlated to quantifiable behavior. In this study, the structural alterations in one diencephalic dopaminergic nucleus induced by 1-methyl-4-phenylpyridinium (MPP+), a toxin inducing Parkinson's disease in humans, and those found in several neuronal groups after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the pretoxin, were associated with decreased swimming speed. Detailed cell counts of dopaminergic groups indicated a transient decline of tyrosine hydroxylase expressing neurons up to about 50% after MPTP. The MPTP effect was partly sensitive to monoamine oxidase inhibitor deprenyl. Detailed analysis of the developing catecholaminergic cell groups suggests that the cell groups emerged at their final positions and no obvious significant migration from the original positions was seen. One 5-HT neuron group was also affected by MPTP treatment, whereas other groups remained intact, suggesting that the effect is selective. New nomenclature for developing catecholaminergic cell groups corresponding to adult groups is introduced. The diencephalic cell population consisting of groups 5,6 and 11 was sensitive to both MPTP and MPP+ and in this respect resembles mammalian substantia nigra. The results suggest that MPTP and MPP+ induce a transient functional deficit and motility disorder in larval zebrafish.