Characterisation of behavioural and neurodegenerative changes induced by intranigral 6-hydroxydopamine lesions in a mouse model of Parkinson's disease
Characterisation of behavioural and neurodegenerative changes induced by intranigral 6-hydroxydopamine lesions in a mouse model of Parkinson's disease
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DOI：
10.1111/j.1460-9568.2010.07265.x
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发表时间：
2010-06-01
影响因子：
3.4
通讯作者：
Bjorklund, Anders
中科院分区：
文献类型：
--
作者：
Grealish, Shane;Mattsson, Bengt;Bjorklund, Anders
尽管广泛使用小鼠作为帕金森病模型，但令人惊讶的是缺乏对小鼠单侧病变模型的验证和表征以及由这种病变诱导的行为障碍的程度。本研究的目的是观察6-羟基多巴胺单方面注射到黑质后观察到的行为缺陷，并与行为障碍的损害程度纹状体多巴胺能通路。我们发现最近引入的用于评估感觉运动损伤的测试，走廊任务，在确定病变严重程度方面特别有用，并且该测试与标准药物诱导的旋转测试相结合，可用于选择具有深度（>= 80%）多巴胺能病变且随时间推移稳定的动物。基于这些数据，我们提出的标准，可用于预测病变的程度，分为严重，中度或轻度病变的中纹状体通路。细胞损失和纹状体神经支配与每个测试中的性能的相关性为神经恢复和细胞移植研究中的功能恢复的评估以及干细胞衍生的多巴胺神经元制剂的体内功效和性能的评价提供了有用的工具。
Despite the widespread use of mice as models of Parkinson's disease there is a surprising lack of validation and characterisation of unilateral lesion models in mice and the extent of behavioural impairments induced by such lesions. The aim of the present study was to characterise the behavioural deficits observed after injection of 6-hydroxydopamine unilaterally into the substantia nigra, and correlate the behavioural impairments with the extent of damage to the mesostriatal dopaminergic pathway. We found that a recently introduced test for assessment of sensorimotor impairment, the corridor task, was particularly useful in determining lesion severity, and that this test, in combination with standard drug-induced rotation tests, can be used to select animals with profound (>= 80%) dopaminergic lesions that are stable over time. Based on these data we propose criteria that can be used to predict the extent of lesion, classified as severe, intermediate or mild lesions of the mesostriatal pathway. The correlation of cell loss and striatal innervation with the performance in each test provides a useful tool for the assessment of functional recovery in neurorestoration and cell transplantation studies, and for the evaluation of the in vivo efficacy and performance of stem cell-derived dopamine neuron preparations.