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Syndecan-3 contributes to the regulation of the microenvironment at the node of Ranvier following end-to‑side neurorrhaphy: sodium image analysis

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Abstract

Syndecan-3 (SDC3) and Syndecan-4 (SDC4) are distributed throughout the nervous system (NS) and are favourable factors in motor neuron development. They are also essential for regulation of neurite outgrowth in the CNS. However, their roles in the reconstruction of the nodes of Ranvier after peripheral nerve injury (PNI) are still unclear. Present study used an in vivo model of end-to-side neurorrhaphy (ESN) for 1–3 months. The recovery of neuromuscular function was evaluated by grooming test. Expression and co-localization of SDC3, SDC4, and Nav1.6 channel (Nav1.6) at regenerating axons were detected by proximity ligation assay and confocal microscopy after ESN. Time-of-flight secondary ion mass spectrometry was used for imaging ions distribution on tissue. Our data showed that the re-clustering of sodium and Nav1.6 at nodal regions of the regenerating nerve corresponded to the distribution of SDC3 after ESN. Furthermore, the re-establishment of sodium and Nav1.6 correlated with the recovery of muscle power 3 months after ESN. This study suggested syndecans may involve in stabilizing Nav1.6 and further modulate the distribution of sodium at nodal regions after remyelination. The efficiency of sodium re-clustering was improved by the assistance of anionic syndecan, resulting in a better functional repair of PNI.

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Abbreviations

SDC3:

Syndecan-3

SDC4:

Syndecan-4

CMAP:

Compound muscle action potential

ESN:

End-to-side neurorrhaphy

McN:

Musculocutaneous nerve

UN:

Ulnar nerve

TOF–SIMS:

Time-of-flight secondary ion mass spectrometry

PNI:

Peripheral nerve injury

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Acknowledgements

This study was supported by research grants to Dr. Wen-Chieh Liao and Dr. Chiung-Hui Liu from the Ministry of Science and Technology, Taiwan, (MOST-108-2320-B-040-013-, 109-2320-B-040-009-, and 109-2320-B-040-007-MY3). Cryostatting (CM3050S, Leica 149 Microsystems) was performed in the Instrument Center of Chung Shan Medical University, which was supported by Ministry of Science and Technology, Ministry of Education, and Chung Shan Medical University.

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Chiung-hui Liu and Yu-chen Kuo conceived of the study, performed image analysis; and participated in the redaction of the manuscript. Che-Wu Wan and Chao-Chun Hsug carried out immunobloots on nerve tissue. Ying-Jui Ho and Yun-Chi Chiang performed immunocytochemistry experiments on repaired nerves. Fu‑Der Mai and Wei-Jhih Lin participated in the TOF–SIMS analysis. Wen-Chieh, Liao participated in the design and coordination of the study, and drafted the manuscript. All authors read and approved the manuscript.

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Correspondence to Wen-Chieh Liao.

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Liu, CH., Kuo, YC., Wang, CY. et al. Syndecan-3 contributes to the regulation of the microenvironment at the node of Ranvier following end-to‑side neurorrhaphy: sodium image analysis. Histochem Cell Biol 155, 355–367 (2021). https://doi.org/10.1007/s00418-020-01936-z

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  • DOI: https://doi.org/10.1007/s00418-020-01936-z

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