Alterations in neuronal metabolism contribute to the pathogenesis of prion disease

Bourgognon, Julie-Myrtille; Spiers, Jereme G.; Scheiblich, Hannah; Antonov, Alexey; Bradley, Sophie J.; Tobin, Andrew B.; Steinert, Joern R.

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.

Citation

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

• Journal Article Type: Article
• Acceptance Date: Jun 4, 2018
• Online Publication Date: Jun 18, 2018
• Publication Date: 2018-08
• Deposit Date: Jun 17, 2020
• Journal: Cell Death and Differentiation
• Print ISSN: 1350-9047
• Electronic ISSN: 1476-5403
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 25
• Issue: 8
• Pages: 1408-1425
• DOI: https://doi.org/10.1038/s41418-018-0148-x
• Public URL: https://nottingham-repository.worktribe.com/output/4667970
• Publisher URL: https://www.nature.com/articles/s41418-018-0148-x
• Additional Information: Received: 22 January 2018; Revised: 14 May 2018; Accepted: 4 June 2018; First Online: 18 June 2018; : ; : The authors declare that they have no conflict of interest.