Choi Yoon Jung, Chae Sukyung, Kim Jeong Hun, Barald Kate F, Park Joong Yull, Lee Sang-Hoon
Department of Biomedical Engineering, College of Health Science, Korea University, Seoul, Republic of Korea.
Sci Rep. 2013;3:1921. doi: 10.1038/srep01921.
Alzheimer's disease is accompanied by progressive, time-dependent changes of three moieties of amyloid beta. In vitro models therefore should provide same conditions for more physiologic studies. Here we observed changes in the number of fibrils over time and studied the correlation between amyloid beta moieties and neurotoxicity. Although the number of fibrils increased dramatically, the change in neurotoxicity with time was small, suggesting that fibrils make little contribution to neurotoxicity. To study the neurotoxicity of diffusible moieties by regulating microenvironments, we created a bio-mimetic microfluidic system generating spatial gradients of diffusible oligomeric assemblies and assessed their effects on cultured neurons. We found amyloid beta exposure produced an atrophy effect and observed neurite extension during the differentiation of neural progenitor cells increased when cells were cultured with continuous flow. The results demonstrate the potential neurotoxicity of oligomeric assemblies and establish a prospective microfluidic platform for studying the neurotoxicity of amyloid beta.
阿尔茨海默病伴随着β淀粉样蛋白三个部分的渐进性、时间依赖性变化。因此，体外模型应为更具生理学意义的研究提供相同条件。在此，我们观察了原纤维数量随时间的变化，并研究了β淀粉样蛋白各部分与神经毒性之间的相关性。尽管原纤维数量急剧增加，但神经毒性随时间的变化很小，这表明原纤维对神经毒性的贡献很小。为了通过调节微环境来研究可扩散部分的神经毒性，我们创建了一个仿生微流控系统，该系统可产生可扩散寡聚体组装体的空间梯度，并评估它们对培养神经元的影响。我们发现β淀粉样蛋白暴露会产生萎缩效应，并观察到当神经祖细胞在连续流动条件下培养时，其分化过程中的神经突延伸增加。这些结果证明了寡聚体组装体潜在的神经毒性，并建立了一个用于研究β淀粉样蛋白神经毒性的前瞻性微流控平台。
