Open AccessKey Glycolytic Metabolites in Paralyzed Skeletal Muscle Are Altered Seven Days after Spinal Cord Injury in Mice
Author(s) -
Zachary Graham,
Jacob A. Siedlik,
Lauren Harlow,
Karim Sahbani,
William A. Bauman,
Hesham A. Tawfeek,
Christopher P. Cardozo
Publication year - 2019
Publication title -
journal of neurotrauma
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.653
H-Index - 149
eISSN - 1557-9042
pISSN - 0897-7151
DOI - 10.1089/neu.2018.6144
Subject(s) - glycolysis , skeletal muscle , spinal cord injury , monocarboxylate transporter , medicine , endocrinology , lactic acid , spinal cord , pyruvic acid , carbohydrate metabolism , anaerobic glycolysis , glucose transporter , ketone bodies , pyruvate dehydrogenase complex , metabolism , biochemistry , biology , transporter , insulin , enzyme , gene , genetics , psychiatry , bacteria
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.