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首页> 外文期刊>The European Journal of Neuroscience >The mouse MPTP model: gene expression changes in dopaminergic neurons.
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The mouse MPTP model: gene expression changes in dopaminergic neurons.

机译：小鼠MPTP模型：多巴胺能神经元的基因表达发生变化。

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Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Although valuable animal models have been developed, our knowledge of the aetiology and pathogenic factors implicated in PD is still insufficient to develop causal therapeutic strategies aimed at halting its progression. The neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is one of the most valuable models for analysing pathological aspects of PD. In this paper we studied the gene expression patterns underlying the pathogenesis of MPTP-induced neurodegeneration. We treated young and old C57BL/6 mice with different schedules of MPTP to induce degenerative processes that vary in intensity and time-course. During the first week after intoxication we used nonradioactive in situ-hybridization to investigate the expression patterns of genes associated with (i) dopamine metabolism and signalling; (ii) familial forms of PD; (iii) protein folding and (iv) energy metabolism. MPTP injections induced different severities of neuronal injury depending on the age of the animals and the schedule of administration as well as a significant degeneration in the striatum. In situ hybridization showed that MPTP intoxication initiated a number of gene expression changes that (i) were restricted to the neurons of the substantia nigra pars compacta; (ii) were correlated in intensity and number of changes with the age of the animals and the severity of histopathological disturbances; (iii) displayed in each a significant down-regulation by the end of one week after the last MPTP injection, but (iv) varied within one MPTP regimen in expression levels during the observation period. The subacute injection of MPTP into one-year-old mice induced the most severe changes in gene expression. All genes investigated were affected. However, alpha-synuclein was the only gene that was exclusively up-regulated in MPTP-treated animals displaying cell death.
机译：帕金森氏病（PD）是一种常见的神经退行性疾病，其特征是黑质中多巴胺能神经元的逐渐丧失。尽管已经开发了有价值的动物模型，但我们对PD所涉及的病因和致病因素的了解仍不足以开发旨在阻止其进展的因果治疗策略。 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的神经毒性是分析PD病理方面最有价值的模型之一。在本文中，我们研究了MPTP诱导的神经退行性病变发病机制的基因表达模式。我们用不同的MPTP方案对年轻和老龄C57BL / 6小鼠进行了处理，以诱导其强度和时间变化的变性过程。在中毒后的第一周，我们使用非放射性原位杂交技术来研究与（i）多巴胺代谢和信号传导相关的基因的表达模式; （ii）PD的家族形式; （iii）蛋白质折叠和（iv）能量代谢。 MPTP注射会引起不同程度的神经损伤，具体取决于动物的年龄和给药计划以及纹状体的严重变性。原位杂交表明，MPTP中毒引发了许多基因表达变化，这些变化是：（i）限于黑质致密部的神经元; （ii）强度和变化数量与动物的年龄以及组织病理学疾病的严重程度相关; （iii）在最后一次MPTP注射后的一周内，每种药物均显示出明显的下调，但（iv）在观察期内，一种MPTP方案内的表达水平有所不同。向一岁大小鼠亚急性注射MPTP导致基因表达发生最严重的变化。研究的所有基因均受影响。但是，α-突触核蛋白是唯一在被MPTP处理的动物中显示细胞死亡的基因中唯一被上调的基因。

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