Impaired Pentose Phosphate Pathway in the Spinal Cord of the hSOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

  • Tesfaye Wolde Tefera
  • Katherine Bartlett
  • Shirley S. Tran
  • Mark P. Hodson
  • Karin BorgesEmail author


Impairments in energy metabolism in amyotrophic lateral sclerosis (ALS) have long been known. However, the changes in the energy-producing pathways in ALS are not comprehensively understood. To investigate specific alterations in glucose metabolism in glycolytic, pentose phosphate, and TCA cycle pathways, we injected uniformly labeled [U-13C]glucose to wild-type and hSOD1G93A mice at symptom onset (80 days). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), levels of metabolites were determined in extracts of the cortex and spinal cord. In addition, the activities of several enzymes involved in glucose metabolism were quantified. In the spinal cord, the levels of pentose phosphate pathway (PPP) intermediate ribose 5-phosphate (p = 0.037) were reduced by 37% in hSOD1G93A mice, while the % 13C enrichments in glucose 6-phosphate were increased threefold. The maximal activities of the enzyme glucose 6-phosphate dehydrogenase were decreased by 24% in the spinal cord (p = 0.005), suggesting perturbations in the PPP. The total amount of pyruvate in the cortex (p = 0.039) was reduced by 20% in hSOD1G93A mice. Also, the activities of the glycolytic enzyme pyruvate kinase were reduced in the cortex by 31% (p = 0.002), indicating alterations in glycolysis. No significant differences were seen in the total amounts as well as % 13C enrichments in most TCA cycle intermediates, suggesting largely normal TCA cycle function. On the other hand, oxoglutarate dehydrogenase activity was decreased in the cortex, which may indicate increased oxidative stress. Overall, this study revealed decreased activity of the PPP in the spinal cord and alterations in glycolysis in hSOD1G93A mouse CNS tissues at the early symptomatic stage of disease.


Energy metabolism Glycolysis Liquid chromatography-tandem mass spectrometry Motor neuron disease Pentose phosphate pathway TCA cycle 



We wish to thank the Queensland Brain Institute and Dr. Shuyan Ngo for providing animals. TWT is a recipient of The University of Queensland International scholarship.


This work was supported by the Motor Neurone Disease Research Institute Australia to KB (grant number: GIA 1704).

Compliance with Ethical Standards

All animal experiments were approved by the University of Queensland Animal Ethics Committee (SBMS 128/14) and followed the guidelines of the Queensland Animal Care and Protection Act 2001.

Conflict of Interest

The authors declare that they have no conflicts of interest.

Supplementary material

12035_2019_1485_MOESM1_ESM.docx (20 kb)
Supplementary Table 1 (DOCX 19 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Neurological Disorders and Metabolism Lab, School of Biomedical SciencesThe University of QueenslandBrisbaneAustralia
  2. 2.Australian Institute for Bioengineering and NanotechnologyThe University of QueenslandBrisbaneAustralia
  3. 3.Metabolomics Australia Queensland Node, Australian Institute for Bioengineering and NanotechnologyThe University of QueenslandBrisbaneAustralia
  4. 4.School of PharmacyThe University of QueenslandBrisbaneAustralia
  5. 5.Metabolomics Research LaboratoryVictor Chang Cardiac Research InstituteSydneyAustralia

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