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

BMC Research Notes

Paul C Guest¹  Sabine Bahn²  Hassan Rahmoune¹  Bob Amess¹  Pieter J Peeters³  Ilse Lenaerts³  Nancy Aerts³  Laura W Harris¹  Agnes Ernst¹  Murtada Alsaif¹  Daniel Martins-de-Souza¹ 

[1]Dept of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QT, UK

[2]Dept of Neuroscience, Erasmus Medical Centre, Rotterdam, The Netherlands

[3]Janssen Research & Development, Division of Janssen Pharmaceutica N.V, Beerse, Belgium

关键词: Selective reaction monitoring;    Multiple reaction monitoring;    Glycolysis;    Assay;    Preclinical;    Proteomics;    Schizophrenia;    Multiplex;    MRM;    SRM;   

Others  :  1166583
DOI  :  10.1186/1756-0500-5-146

 received in 2011-12-17, accepted in 2012-03-15,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Martins-de-Souza et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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