期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：45
DOI：10.1073/pnas.2106143118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
The high spatial resolution of three-dimensional (3D) fluorescence imaging of myelinated fibers will greatly facilitate the understanding of 3D neural networks and the pathophysiology of demyelinating diseases. However, existing myelin probes are far from satisfactory because of their low–signal-to-background ratio and poor tissue permeability. We herein developed a near-infrared aggregation-induced emission-active probe, PM-ML, for high-performance myelin imaging. PM-ML could specifically image myelinated fibers in teased sciatic nerves and mouse brain tissues with high contrast, good photostability, and deep penetration depth. PM-ML staining is compatible with several tissue-clearing methods. Its application in assessing myelination for neuropathological studies was also demonstrated using a multiple sclerosis mouse model.
Myelin, the structure that surrounds and insulates neuronal axons, is an important component of the central nervous system. The visualization of the myelinated fibers in brain tissues can largely facilitate the diagnosis of myelin-related diseases and understand how the brain functions. However, the most widely used fluorescent probes for myelin visualization, such as Vybrant DiD and FluoroMyelin, have strong background staining, low-staining contrast, and low brightness. These drawbacks may originate from their self-quenching properties and greatly limit their applications in three-dimensional (3D) imaging and myelin tracing. Chemical probes for the fluorescence imaging of myelin in 3D, especially in optically cleared tissue, are highly desirable but rarely reported. We herein developed a near-infrared aggregation-induced emission (AIE)-active probe, PM-ML, for high-performance myelin imaging. PM-ML is plasma membrane targeting with good photostability. It could specifically label myelinated fibers in teased sciatic nerves and mouse brain tissues with a high–signal-to-background ratio. PM-ML could be used for 3D visualization of myelin sheaths, myelinated fibers, and fascicles with high-penetration depth. The staining is compatible with different brain tissue–clearing methods, such as
Clear
T
and
Clear
T2
. The utility of PM-ML staining in demyelinating disease studies was demonstrated using the mouse model of multiple sclerosis. Together, this work provides an important tool for high-quality myelin visualization across scales, which may greatly contribute to the study of myelin-related diseases.
