Ultramicroscopy Reveals Axonal Transport Impairments in Cortical Motor Neurons at Prion Disease
Ultramicroscopy Reveals Axonal Transport Impairments in Cortical Motor Neurons at Prion Disease
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DOI：
10.1016/j.bpj.2009.01.032
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发表时间：
2009-04-22
影响因子：
3.4
通讯作者：
Flechsig, Eckhard
中科院分区：
文献类型：
--
作者：
Ermolayev, Vladimir;Friedrich, Mike;Flechsig, Eckhard
中枢神经系统神经元回路的功能成像对于神经退行性疾病的表型筛选或缺陷调查至关重要。目前的技术要么穿透深度低，分辨率差，要么受动物年龄的限制。在这里，我们提出了一种新的荧光成像和三维重建在成年小鼠中枢神经系统的超微协议。结合示踪作为轴突运输的功能测定，逆行标记的下行运动神经元以> 4mm的穿透深度可视化。在临床朊病毒病发作前不久对运动皮层的分析显示，>80%的神经元在轴突运输方面存在功能障碍。我们的研究提供的证据表明，朊病毒病与严重的轴突运输缺陷在皮层运动神经元，并提出了一种新的机制朊病毒介导的神经变性。
The functional imaging of neuronal circuits of the central nervous system is crucial for phenotype screenings or investigations of defects in neurodegenerative disorders. Current techniques yield either low penetration depth, yield poor resolution, or are restricted by the age of the animals. Here, we present a novel ultramicroscopy protocol for fluorescence imaging and three-dimensional reconstruction in the central nervous system of adult mice. In combination with tracing as a functional assay for axonal transport, retrogradely labeled descending motor neurons were visualized with >4 mm penetration depth. The analysis of the motor cortex shortly before the onset of clinical prion disease revealed that >80% neurons have functional impairments in axonal transport. Our study provides evidence that prion disease is associated with severe axonal transport defects in the cortical motor neurons and suggests a novel mechanism for prion-mediated neurodegeneration.