Key glycolytic metabolites in paralyzed skeletal muscle are altered seven days after spinal cord injury in Mice

Zachary A. Graham, Jacob A. Siedlik, Lauren Harlow, Karim Sahbani, William A. Bauman, Hesham A. Tawfeek, Christopher P. Cardozo

Research output: Contribution to journalArticle

Abstract

Spinal cord injury (SCI) results in rapid muscle atrophy and an oxidative-to-glycolytic fiber-type shift. Those with chronic SCI are more at risk for developing insulin resistance and reductions in glucose clearance than able-bodied individuals, but how glucose metabolism is affected after SCI is not well known. An untargeted metabolomics approach was utilized to investigate changes in whole-muscle metabolites at an acute (7-day) and subacute (28-day) time frame after a complete T9 spinal cord transection in 20-week-old female C57BL/6 mice. Two hundred one metabolites were detected in all samples, and 83 had BinBase IDs. A principal components analysis showed the 7-day group as a unique cluster. Further, 36 metabolites were altered after 7- and/or 28-day post-SCI (p values <0.05), with 12 passing further false discovery rate exclusion criteria; of those 12 metabolites, three important glycolytic molecules - glucose and downstream metabolites pyruvic acid and lactic acid - were reduced at 7 days compared to those values in sham and/or 28-day animals. These changes were associated with altered expression of proteins associated with glycolysis, as well as monocarboxylate transporter 4 gene expression. Taken together, our data suggest an acute disruption of skeletal muscle glucose uptake at 7 days post-SCI, which leads to reduced pyruvate and lactate levels. These levels recover by 28 days post-SCI, but a reduction in pyruvate dehydrogenase protein expression at 28 days post-SCI implies disruption in downstream oxidation of glucose.

Original languageEnglish (US)
Pages (from-to)2722-2731
Number of pages10
JournalJournal of Neurotrauma
Volume36
Issue number18
DOIs
StatePublished - Sep 15 2019

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

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