The application of selective reaction monitoring confirms dysregulation of glycolysis in a preclinical model of schizophrenia

Autor: Hassan Rahmoune, Sabine Bahn, Paul C. Guest, Laura W. Harris, Daniel Martins-de-Souza, Nancy Aerts, Ilse Lenaerts, Murtada Alsaif, Bob Amess, Agnes Ernst, Pieter J. Peeters
Přispěvatelé: Apollo - University of Cambridge Repository
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Male
Proteomics
Multiple reaction monitoring
Fructose-bisphosphate aldolase
Phencyclidine
Assay
lcsh:Medicine
Pharmacology
chemistry.chemical_compound
Phosphoglycerate Mutase 1
Fructose-Bisphosphate Aldolase
Hexokinase
Phosphoglycerate kinase 1
lcsh:QH301-705.5
Multiplex
Medicine(all)
Phosphoglycerate Mutase
education.field_of_study
Glyceraldehyde-3-Phosphate Dehydrogenases
General Medicine
Preclinical
Frontal Lobe
Biochemistry
Schizophrenia
MRM
Glycolysis
Metabolic Networks and Pathways
Research Article
Triose-Phosphate Isomerase
SRM
Biology
General Biochemistry
Genetics and Molecular Biology
Selective reaction monitoring
Phosphoglycerate mutase
medicine
Animals
Humans
education
lcsh:Science (General)
Phosphoglycerate kinase
Biochemistry
Genetics and Molecular Biology(all)
lcsh:R
medicine.disease
Rats
Enolase 2
Disease Models
Animal
Phosphoglycerate Kinase
chemistry
lcsh:Biology (General)
Phosphopyruvate Hydratase
Multivariate Analysis
biology.protein
lcsh:Q1-390
Zdroj: BMC Research Notes, Vol 5, Iss 1, p 146 (2012)
BMC Research Notes
Popis: Background: Establishing preclinical models is essential for novel drug discovery in schizophrenia. Most existing models are characterized by abnormalities in behavioral readouts, which are informative, but do not necessarily translate to the symptoms of the human disease. Therefore, there is a necessity of characterizing the preclinical models from a molecular point of view. Selective reaction monitoring (SRM) has already shown promise in preclinical and clinical studies for multiplex measurement of diagnostic, prognostic and treatment-related biomarkers. Methods: We have established an SRM assay for multiplex analysis of 7 enzymes of the glycolysis pathway which is already known to be affected in human schizophrenia and in the widely-used acute PCP rat model of schizophrenia. The selected enzymes were hexokinase 1 (Hk1), aldolase C (Aldoc), triosephosphate isomerase (Tpi1), glyceraldehyde-3-phosphate dehydrogenase (Gapdh), phosphoglycerate mutase 1 (Pgam1), phosphoglycerate kinase 1 (Pgk1) and enolase 2 (Eno2). The levels of these enzymes were analyzed using SRM in frontal cortex from brain tissue of PCP treated rats. Results: Univariate analyses showed statistically significant altered levels of Tpi1 and alteration of Hk1, Aldoc, Pgam1 and Gapdh with borderline significance in PCP rats compared to controls. Most interestingly, multivariate analysis which considered the levels of all 7 enzymes simultaneously resulted in generation of a bi-dimensional chart that can distinguish the PCP rats from the controls. Conclusions: This study not only supports PCP treated rats as a useful preclinical model of schizophrenia, but it also establishes that SRM mass spectrometry could be used in the development of multiplex classification tools for complex psychiatric disorders such as schizophrenia.
Databáze: OpenAIRE
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