Dopaminergic Neuron-Specific Autophagy-Deficient Mice
Dopaminergic Neuron-Specific Autophagy-Deficient Mice
复制标题
多巴胺能神经元特异性自噬缺陷小鼠
DOI：
10.1007/7651_2018_156
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Hattori N.
中科院分区：
文献类型：
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作者：
Sato S;Hattori N.
目前没有一种遗传性帕金森病（PD）小鼠模型能概括PD的所有特征。此外，这些模型中只有少数发生轻度多巴胺（DA）神经变性。对于遗传性PD模型中缺乏DA神经退行性变的最简单的解释是一种补偿机制，这种机制是由发育过程中的适应性变化引起的，因此很难在小鼠的整个生命周期内观察到退行性表型。在这里，我们描述DA神经元特异性自噬缺陷小鼠，并提供体内证据路易体形成。Atg7缺陷型小鼠表现出典型的Lewy病理学，包括内源性突触核蛋白和神经元丢失，类似于PD。此外，DA水平受到多巴胺能神经元损失的影响。DA神经元中与年龄相关的运动功能障碍和病理学表明，自噬损伤是PD病理学的潜在机制。
None of the current genetic Parkinson’s disease (PD) models in mouse recapitulates all features of PD. Additionally, only a few of these models develop mild dopamine (DA) neurodegeneration. And the most parsimonious explanation for the lack of DA neurodegeneration in genetic PD models is a compensatory mechanism that results from adaptive changes during development, making it hard to observe the degenerative phenotype over the life span of mice. Here, we characterize DA neuron-specific autophagy-deficient mice and provide in vivo evidence for Lewy body formation. Atg7-deficient mice demonstrate typical Lewy pathology, including endogenous synuclein and neuronal loss, which resembles PD. Furthermore DA levels are affected by dopaminergic neuronal loss. The age-related motor dysfunction and pathology in DA neurons suggest that impairment of autophagy is a potential mechanism underlying the pathology of PD.