ACS Chem Neurosci. 2012 Jun 20;3(6):433-8. doi: 10.1021/cn3000026.
Mitochondria, synaptic vesicles, and other cytoplasmic constituents have to travel long distance along the axons from cell bodies to nerve terminals. Interruption of this axonal transport may contribute to many neurodegenerative diseases including Alzheimer's disease (AD). It has been recently shown that exposure of cultured neurons to β-amyloid (Aβ) resulted in severe impairment of mitochondrial transport. This Letter describes an integrated microfluidic platform that establishes surface patterned and compartmentalized culture of neurons for studying the effect of Aβ on mitochondria trafficking in full length of axons. We have successfully quantified the trafficking of fluorescently labeled mitochondria in distal and proximal axons using image processing. Selective treatment of Aβ in the somal or axonal compartments resulted in considerable decrease in mitochondria movement in a location dependent manner such that mitochondria trafficking slowed down more significantly proximal to the location of Aβ exposure. Furthermore, this result suggests a promising application of microfluidic technology for investigating the dysfunction of axonal transport related to neurodegenerative diseases.
线粒体、突触小泡和其他细胞质成分必须沿着轴突从细胞体长途运输到神经末梢。这种轴突运输的中断可能导致许多神经退行性疾病,包括阿尔茨海默病(AD)。最近的研究表明,培养的神经元暴露于β-淀粉样蛋白(Aβ)会导致线粒体运输严重受损。这封信描述了一个集成的微流控平台,该平台建立了神经元的表面图案化和分隔培养,用于研究 Aβ对全长轴突中线粒体运输的影响。我们已经成功地使用图像处理量化了荧光标记的线粒体在远端和近端轴突中的运输。在体部或轴突隔室中选择性地处理 Aβ会导致线粒体运动以位置依赖的方式显著减少,使得线粒体运输在 Aβ暴露位置附近更显著地减慢。此外,这一结果表明微流控技术在研究与神经退行性疾病相关的轴突运输功能障碍方面具有广阔的应用前景。