Fang Yuqiang, Iu Catherine Y Y, Lui Cathy N P, Zou Yukai, Fung Carmen K M, Li Hung Wing, Xi Ning, Yung Ken K L, Lai King W C
Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong.
Department of Biology, Hong Kong Baptist University, Kowloon, Hong Kong.
Sci Rep. 2014 Nov 17;4:7074. doi: 10.1038/srep07074.
Glutamate-mediated neurodegeneration resulting from excessive activation of glutamate receptors is recognized as one of the major causes of various neurological disorders such as Alzheimer's and Huntington's diseases. However, the underlying mechanisms in the neurodegenerative process remain unidentified. Here, we investigate the real-time dynamic structural and mechanical changes associated with the neurodegeneration induced by the activation of N-methyl-D-aspartate (NMDA) receptors (a subtype of glutamate receptors) at the nanoscale. Atomic force microscopy (AFM) is employed to measure the three-dimensional (3-D) topography and mechanical properties of live SH-SY5Y cells under stimulus of NMDA receptors. A significant increase in surface roughness and stiffness of the cell is observed after NMDA treatment, which indicates the time-dependent neuronal cell behavior under NMDA-mediated neurodegeneration. The present AFM based study further advance our understanding of the neurodegenerative process to elucidate the pathways and mechanisms that govern NMDA induced neurodegeneration, so as to facilitate the development of novel therapeutic strategies for neurodegenerative diseases.
由谷氨酸受体过度激活介导的谷氨酸能神经变性被认为是诸如阿尔茨海默病和亨廷顿病等各种神经疾病的主要病因之一。然而，神经变性过程中的潜在机制仍不明晰。在此，我们在纳米尺度上研究与N-甲基-D-天冬氨酸（NMDA）受体（谷氨酸受体的一种亚型）激活所诱导的神经变性相关的实时动态结构和力学变化。采用原子力显微镜（AFM）来测量在NMDA受体刺激下活的SH-SY5Y细胞的三维（3-D）形貌和力学性能。在NMDA处理后观察到细胞表面粗糙度和硬度显著增加，这表明在NMDA介导的神经变性过程中神经元细胞行为具有时间依赖性。目前基于AFM的研究进一步推进了我们对神经变性过程的理解，以阐明控制NMDA诱导神经变性的途径和机制，并促进神经变性疾病新型治疗策略的开发。
