Alterations in neuronal metabolism contribute to the pathogenesis of prion disease

Bourgognon, J.-M. , Spiers, J. G., Scheiblich, H., Antonov, A., Bradley, S. J. , Tobin, A. B. and Steinert, J. R. (2018) Alterations in neuronal metabolism contribute to the pathogenesis of prion disease. Cell Death and Differentiation, 25(8), pp. 1408-1425. (doi:10.1038/s41418-018-0148-x) (PMID:29915278) (PMCID:PMC6113283)

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Abstract

Neurodegenerative conditions are characterised by a progressive loss of neurons, which is believed to be initiated by misfolded protein aggregations. During this time period, many physiological and metabolomic alterations and changes in gene expression contribute to the decline in neuronal function. However, these pathological effects have not been fully characterised. In this study, we utilised a metabolomic approach to investigate the metabolic changes occurring in the hippocampus and cortex of mice infected with misfolded prion protein. In order to identify these changes, the samples were analysed by ultrahigh-performance liquid chromatography-tandem mass spectroscopy. The present dataset comprises a total of 498 compounds of known identity, named biochemicals, which have undergone principal component analysis and supervised machine learning. The results generated are consistent with the prion-inoculated mice having significantly altered metabolic profiles. In particular, we highlight the alterations associated with the metabolism of glucose, neuropeptides, fatty acids, L-arginine/nitric oxide and prostaglandins, all of which undergo significant changes during the disease. These data provide possibilities for future studies targeting and investigating specific pathways to better understand the processes involved in neuronal dysfunction in neurodegenerative diseases.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bourgognon, Dr Julie-Myrtille and Tobin, Andrew and Bradley, Dr Sophie
Authors: Bourgognon, J.-M., Spiers, J. G., Scheiblich, H., Antonov, A., Bradley, S. J., Tobin, A. B., and Steinert, J. R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
Journal Name:Cell Death and Differentiation
Publisher:Nature Publishing Group
ISSN:1350-9047
ISSN (Online):1476-5403
Published Online:18 June 2018

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
750161Collaborative Network to Define the Molecular Determinants of G Protein Coupled Receptor Clinical EfficacyAndrew TobinWellcome Trust (WELLCOTR)201529/Z/16/ZRI MOLECULAR CELL & SYSTEMS BIOLOGY
750711MICA Pharmacological, molecular and cellular mechanisms of muscarinic slowing (modification) of neurodegenerative disease.Andrew TobinMedical Research Council (MRC)MR/P019366/1RI MOLECULAR CELL & SYSTEMS BIOLOGY