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足部失误测试作为帕金森病6-羟基多巴胺大鼠模型中的一种筛查工具。

The footfault test as a screening tool in the 6-hydroxydopamine rat model of Parkinson's disease.

作者信息

Silvestrin Roberta Bristot, de Oliveira Lucas Fürstenau, Batassini Cristiane, Oliveira Alcyr, e Souza Tadeu Mello

机构信息

Programa de Pós-Graduação em Neurociências - ICBS, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, Sala 107, CEP 90.046-900, Porto Alegre, RS, Brazil.

出版信息

J Neurosci Methods. 2009 Mar 15;177(2):317-21. doi: 10.1016/j.jneumeth.2008.10.030. Epub 2008 Nov 6.

DOI:10.1016/j.jneumeth.2008.10.030
PMID:19026686
Abstract

The administration of 6-hydroxydopamine (6-OHDA) into the nigrostriatal pathway is a rat model of Parkinson's disease (PD). The footfault test is a behavioural task in which rodents have their motor functions assessed. Here, we observed that unilaterally 6-OHDA-lesioned animals show a context-induced ipsilateral rotational behaviour when placed on the footfault apparatus for 3 min and this may be used as index to detect lesioned animals. Our results showed a sensitivity and specificity of 100% for lesions higher than 94% and 64%, respectively (ROC curve: AUC=0.988). A binary logistic regression model showed an expB=1.116 (95% CI, 1.007-1.236) and C=-9.081+/-4.554 (p=0.046) using the nigral tyrosine hidroxylase immunocontent as standard (each unit represents a 10%-lesion extension). Additionally, the footfault test was more sensitive than apomorphine challenging at 1mg/kg when these tests were carried out days apart and it was less sensitive than methylphenidate at 40 mg/kg (sign test, p<0.05). Therefore, the footfault test may be very useful in the PD animal model for screening animals since it is fast and simple and it does not require a drug to induce rotational activity.

摘要

向黑质纹状体通路注射6-羟基多巴胺(6-OHDA)是帕金森病(PD)的大鼠模型。足部错误试验是一种评估啮齿动物运动功能的行为任务。在此,我们观察到,单侧6-OHDA损伤的动物在置于足部错误试验装置上3分钟时会出现情境诱导的同侧旋转行为,这可作为检测损伤动物的指标。我们的结果显示,对于损伤高于94%和64%的情况,敏感性和特异性分别为100%(ROC曲线:AUC = 0.988)。以黑质酪氨酸羟化酶免疫含量为标准(每个单位代表10%的损伤范围),二元逻辑回归模型显示expB = 1.116(95%CI,1.007 - 1.236),C = -9.081±4.554(p = 0.046)。此外,当这些试验间隔数天进行时,足部错误试验比1mg/kg的阿扑吗啡激发试验更敏感,而比40mg/kg的哌甲酯试验敏感性更低(符号检验,p < 0.05)。因此,足部错误试验在PD动物模型中筛选动物可能非常有用,因为它快速简便,且不需要药物诱导旋转活动。

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