Abstract
Myelin plays an essential role in the nervous system and its disruption in diseases such as multiple sclerosis may lead to neuronal death, thus causing irreversible functional impairments. Understanding myelin biology is therefore of fundamental and clinical importance, but no tools currently exist to describe the fine spatial organization of myelin sheaths in vivo. Here we demonstrate intravital quantification of the myelin molecular structure using a microscopy method based on polarization-resolved coherent Raman scattering. Developmental myelination was imaged noninvasively in live zebrafish. Longitudinal imaging of individual axons revealed changes in myelin organization beyond the diffraction limit. Applied to promyelination drug screening, the method uniquely enabled the identification of focal myelin regions with differential architectures. These observations indicate that the study of myelin biology and the identification of therapeutic compounds will largely benefit from a method to quantify the myelin molecular organization in vivo.
Highlights
A large myelin-specific contrast is obtained in the central nervous system
Myelin imaging in the spinal cord is possible in wild-type zebrafish, but only after a chemical treatment aiming at removing melanophore pigments as they generate a strong background signal
We found no difference between the two strains by evaluating the axon diameter and the myelin thickness (Supplementary Fig. 1)
Summary
We aimed to evaluate the potential for in vivo drug screening of P-CARS using the Mauthner myelination zebrafish model
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