Biochemistry and Biophysics Reports (Jun 2025)

Metabolism of sphingolipids in a rat spinal cord stenosis model

  • Baasanjav Uranbileg,
  • Yoko Hoshino,
  • Mariko Ezaka,
  • Makoto Kurano,
  • Kanji Uchida,
  • Yutaka Yatomi,
  • Nobuko Ito

DOI
https://doi.org/10.1016/j.bbrep.2025.102025
Journal volume & issue
Vol. 42
p. 102025

Abstract

Read online

Background: Lumbar spinal canal stenosis (LSCS) plays a crucial role in neurogenic claudication and neuropathic pain. Recent studies suggest that changes in sphingolipid metabolism are linked to neuropathic pain. To explore the association between sphingolipids and LSCS, we measured the levels of sphingolipids and sphingolipid-associated molecules in an animal model of cauda equina compression (CEC), a typical type of LSCS. Methods: By placing silicon blocks within the lumbar epidural space, CEC model were constructed in which motor disfunction had already been confirmed in our previous study. Quantitative measurements of various sphingolipids were conducted using LC-MS/MS in spinal cord and cerebrospinal fluid (CSF) samples on days 1, 7, and 28 following insertion of silicon blocks. Additionally, gene expression was analyzed in spinal cord tissue. Results: In the CEC model, there was a significant increase ceramide levels in the CSF with upregulation of ceramide synthase 1 in the spinal cord tissue samples on day 1. Further, S1P levels in the CSF increased on day 7 and in the spinal cord significantly increased on day 28, and there was an increase in mRNA expression levels of sphingosine kinases (SphK)1 on days 1,7, and 28, while SphK2 on days 7 and 28. Regarding S1P receptors, there was an increase in mRNA expression levels of S1P1 on days 1,7, and 28 and S1P3 on day1. Conclusion: The production and activation of the sphingolipid signaling pathway could play a pivotal role in neuropathic pain related to LSCS.

Keywords