Target and untargeted GC–MS based metabolomic study of mouse optic nerve and its potential in the study of neurological visual diseases
Entidad
UAM. Departamento de Biología Molecular; Centro de Biología Molecular Severo Ochoa (CBM)Editor
Elsevier B.V.Fecha de edición
2018-02-10Cita
10.1016/j.jpba.2018.02.015
Journal of Pharmaceutical and Biomedical Analysis 153 (2018): 44-56
ISSN
0731-7085 (print); 1873-264X (online)DOI
10.1016/j.jpba.2018.02.015Financiado por
The authors gratefully acknowledge the financial support from the Spanish Ministry of Economy, Industry and Competitiveness (Grants CTQ2014-55279-R to CB and AG and Grant BFU2015-64829-R to BC), and Fundación Universitaria San Pablo CEU (CGR PhD fellowshipProyecto
Gobierno de España. BFU2015-64829-RVersión del editor
http://doi.org/10.1016/j.jpba.2018.02.015Materias
Metabolomics; Optic neuropathies; GC–MS; Method validation; Fingerprinting; Biología y Biomedicina / BiologíaDerechos
© 2018 Elsevier B.V.Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
Resumen
The optic nerve is made of highly specialized neurons and the energetic supply to their axons is crucial due to their great demand. The energy comes basically through the oxidative phosphorylation in the mitochondria, supported by glial cells metabolism. Mitochondrial dysfunction is a shared feature encountered within the optic neuropathies, including Leber’s Hereditary Optic Neuropathy, Leigh’s Syndrome, or Kjer’s syndrome.
In an effort to investigate the metabolic alterations produced within the optic nerve in a mutant mouse model of Neurological Visual Disease (NVD), a rapid, robust, and efficient one-single phase extraction methodology has been developed and validated for the GC–MS platform. Once the method was successfully validated for lactic acid and pyruvic acid as markers of an adequate optic nerve function, the protocol was applied to unveil the metabolomic signature of the wild-type mouse optic nerve. Along the chromatographic profile of the optic nerve, 94 peaks were identified and, to our knowledge, for the first time. Afterwards, a targeted metabolomics analysis was performed to quantify lactic acid and pyruvic acid in the NDV mice group (n = 8) and its corresponding wild-type (n = 8). Finally, an untargeted metabolomic study was carried out and univariate and multivariate data analyses showed 34 compounds modified in the optic nerve of the mouse with NVD mutation. Then, the metabolic reaction network of the identified metabolites highlighted alterations in the catabolism of proteins, TCA cycle, and urea cycle, reflecting a mitochondrial energetic dysfunction. Taken together, this metabolomic study has proven to be suited for the study of optic neuropathies
Lista de ficheros
Google Scholar:González-Riano, Carolina
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Sanz-Rodríguez, Miriam
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Escudero-Ramirez, Juan
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Lorenzo, M. Paz
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Barbas, Coral
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Cubelos Álvarez, Beatriz
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García, Antonio
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