Stereotaxical infusion of rotenone: a reliable rodent model for Parkinson's disease.
Stereotaxical infusion of rotenone: a reliable rodent model for Parkinson's disease.
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DOI：
10.1371/journal.pone.0007878
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发表时间：
2009-11-18
期刊：
影响因子：
3.7
通讯作者：
Wang T
中科院分区：
文献类型：
--
作者：
Xiong N;Huang J;Zhang Z;Zhang Z;Xiong J;Liu X;Jia M;Wang F;Chen C;Cao X;Liang Z;Sun S;Lin Z;Wang T
帕金森病（PD）的临床相关动物模型可能有助于阐明该疾病的病因，并有助于药物的开发。然而，目前基于神经毒素的模型都不能概括PD的主要临床特征或病理特征，如多巴胺（DA）神经元特异性变性和路易体形成，这限制了这些模型在PD研究中的应用。为了克服这些限制，我们建立了一个大鼠模型，通过立体定向（ST）将小剂量的线粒体复合物- 1抑制剂鱼藤酮注入大脑的两个部位：右侧腹侧被盖区和黑质。在给予ST鱼藤酮4周后，输注侧的酪氨酸羟化酶（TH）免疫反应性下降了43.7%，而全身注射鱼藤酮（SYS）的大鼠免疫反应性下降了75.8%。与对侧相比，鱼藤酮灌注降低了DA含量、谷胱甘肽和超氧化物歧化酶活性，并诱导α -突触核蛋白表达。该ST模型无外周毒性和死亡率，成功率高。因此，基于鱼藤酮的ST模型概括了DA神经元的缓慢和特异性损失，更好地模拟了特发性PD的临床特征，为PD研究提供了一个可靠且与临床更相关的模型。
A clinically-related animal model of Parkinson's disease (PD) may enable the elucidation of the etiology of the disease and assist the development of medications. However, none of the current neurotoxin-based models recapitulates the main clinical features of the disease or the pathological hallmarks, such as dopamine (DA) neuron specificity of degeneration and Lewy body formation, which limits the use of these models in PD research. To overcome these limitations, we developed a rat model by stereotaxically (ST) infusing small doses of the mitochondrial complex-I inhibitor, rotenone, into two brain sites: the right ventral tegmental area and the substantia nigra. Four weeks after ST rotenone administration, tyrosine hydroxylase (TH) immunoreactivity in the infusion side decreased by 43.7%, in contrast to a 75.8% decrease observed in rats treated systemically with rotenone (SYS). The rotenone infusion also reduced the DA content, the glutathione and superoxide dismutase activities, and induced alpha-synuclein expression, when compared to the contralateral side. This ST model displays neither peripheral toxicity or mortality and has a high success rate. This rotenone-based ST model thus recapitulates the slow and specific loss of DA neurons and better mimics the clinical features of idiopathic PD, representing a reliable and more clinically-related model for PD research.
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