组织透明技术在帕金森病中的应用及研究进展

Application and research progress of tissue clearing techniques in Parkinson’s disease

  • 摘要: 帕金森病(PD)是一种常见的神经退行性疾病,其在全球范围内的发病率呈上升趋势,严重影响患者生活质量,给社会和家庭带来沉重负担。然而,迄今为止,国内外研究人员虽付出诸多努力并取得相应研究成果,但仍未探究出针对 PD 的特效治疗办法。其原因可能是PD发病机制复杂,人们对PD患者的异常神经网络认知不足。传统研究方法如二维组织学技术的观察视野和角度较为局限,无法呈现PD的病理全貌。因此,突破二维限制实现三维病理成像对PD的机制探究和开发精准治疗手段具有重要意义。近年来,组织透明技术在中枢神经系统中的应用是神经科学研究中的一个重要突破。它可在不破坏组织结构的情况下观察其内部的细胞和分子的三维结构,实现对PD异常神经网络的结构基础如异常神经元或异常胶质细胞等的可视化,经过光学成像技术对神经环路进行三维重建,从而更准确地描绘神经网络的复杂结构,进而能够更深入地了解PD的病理神经网络,为PD的研究提供了新的视角和方法。文章综述了组织透明技术的成像原理、相比于传统病理技术的优势及其在PD研究中的应用和在多巴胺神经元、神经环路、ɑ-突触核蛋白方面的研究进展,并总结了组织透明技术在PD研究领域的未来展望,旨在为PD的深入研究和有效治疗提供全面的理论依据和技术参考。

     

    Abstract: Parkinson’s disease (PD), a prevalent neurodegenerative disorder, exhibits a rising global incidence. It severely impairs patients’ quality of life and imposes a significant burden on both society and families. However, despite considerable efforts and corresponding research achievements by numerous researchers both domestically and internationally, a specific treatment for PD remains elusive to date. The reason for this may lie in the complex pathogenesis of PD and the insufficient understanding of the abnormal neural networks in PD patients. Traditional research methods, such as two-dimensional histology, are limited in their observational scope and perspective, making it difficult to present a comprehensive pathological picture of PD. Therefore, breaking through the limitations of two-dimensional imaging to achieve three-dimensional pathological visualization holds significant importance for investigating PD’s mechanisms and developing precise treatments. In recent years, the application of tissue clearing techniques in the central nervous system has represented a major breakthrough in neuroscience research. This technique enables the observation of intrinsic cells and molecular structures within tissues in three dimensions without disrupting their architecture. It allows visualization of the structural basis of abnormal neural networks in PD, such as aberrant neurons or glial cells. Combined with optical imaging, tissue clearing facilitates three-dimensional reconstruction of neural circuits, thereby mapping the complex architecture of neural networks with greater accuracy. This approach provides deeper insights into the pathological neural networks in PD, opening up new perspectives and methodologies for its investigation. This review systematically summarizes the imaging principles of tissue clearing techniques, its advantages over traditional pathological techniques, and its applications in PD research—specifically its advancements in studying dopaminergic neurons, neural circuits, and α-synuclein. It concludes with future prospects for this technology in the PD field, aiming to provide a comprehensive theoretical foundation and technical reference for in-depth PD research and the development of effective therapies.

     

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