Issue 7, 2015

1H NMR brain metabonomics of scrapie exposed sheep


While neurochemical metabolite modifications, determined by different techniques, have been diffusely reported in human and mice brains affected by transmissible spongiform encephalopathies (TSEs), this aspect has been little studied in the natural animal hosts with the same pathological conditions so far. Herein, we investigated, by high resolution 1H NMR spectroscopy and multivariate statistical data analysis, the brain metabolite profile of sheep exposed to a scrapie agent in a naturally affected flock. On the basis of clinical examinations and western blotting analysis for the pathological prion protein (PrPSc) in brain tissues, sheep were catalogued as not infected (H), infected with clinical signs (S), and infected without clinical signs (A). By discriminant analysis of spectral data, comparing S vs. H, we found a different metabolite distribution, with inosine, cytosine, creatine, and lactate being higher in S than in H brains, while the branched chain amino acids (leucine, isoleucine, and valine), phenylalanine, uracil, tyrosine, gamma-amino butyric acid, total aspartate (aspartate + N-acetyl aspartate) being lower in S. By a soft independent modelling of class analogy approach, 1 out of 3 A samples was assigned to class H. Furthermore, A brains were found to be higher in choline and choline-containing compounds. By means of partial least squares regression, an excellent correlation was found between the PrPSc amount and the 1H NMR metabolite profile of infected (S and A) sheep, and the metabolite mostly correlated with PrPSc was alanine. The overall results, obtained using different chemometric tools, were able to describe a brain metabolite profile of infected sheep with and without clinical signs, compared to healthy ones, and indicated alanine as a biomarker for PrPSc amounts in scrapie brains.

Graphical abstract: 1H NMR brain metabonomics of scrapie exposed sheep

Article information

Article type
17 Feb 2015
20 Apr 2015
First published
23 Apr 2015
This article is Open Access
Creative Commons BY license

Mol. BioSyst., 2015,11, 2008-2016

Author version available

1H NMR brain metabonomics of scrapie exposed sheep

P. Scano, A. Rosa, A. Incani, C. Maestrale, C. Santucciu, D. Perra, S. Vascellari, A. Pani and C. Ligios, Mol. BioSyst., 2015, 11, 2008 DOI: 10.1039/C5MB00138B

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