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Network analysis of gene expression in mice provides new evidence of involvement of the mTOR pathway in antipsychotic-induced extrapyramidal symptoms

The Pharmacogenomics Journal volume 16, pages 293–300 (2016)Cite this article

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Abstract

To identify potential candidate genes for future pharmacogenetic studies of antipsychotic (AP)-induced extrapyramidal symptoms (EPS), we used gene expression arrays to analyze changes induced by risperidone in mice strains with different susceptibility to EPS. We proposed a systems biology analytical approach that combined the identification of gene co-expression modules related to AP treatment, the construction of protein–protein interaction networks with genes included in identified modules and finally, gene set enrichment analysis of constructed networks. In response to risperidone, mice strain with susceptibility to develop EPS showed downregulation of genes involved in the mammalian target of rapamycin (mTOR) pathway and biological processes related to this pathway. Moreover, we also showed differences in the phosphorylation pattern of the ribosomal protein S6 (rpS6), which is a major downstream effector of mTOR. The present study provides new evidence of the involvement of the mTOR pathway in AP-induced EPS and offers new and valuable markers for pharmacogenetic studies.

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Acknowledgements

This study was supported by the Spanish Ministry of Health, Instituto de Salud Carlos III (FIS, Fondo de Investigacion Sanitaria PI10/02430) and the Catalan Innovation, Universities and Enterprise Authority (Grants DURSI 2014SGR436 and 2014SGR441). We thank the Language Advisory Service of the University of Barcelona, Spain for manuscript revision. The authors also thank Ana Meseguer for sample collection assistance.

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Authors and Affiliations

  1. Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain

    S Mas, P Gassó, D Boloc, N Rodriguez, F Mármol, J Sánchez & A Lafuente

  2. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    S Mas, P Gassó, M Bernardo & A Lafuente

  3. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain

    S Mas, P Gassó, M Bernardo & A Lafuente

  4. Barcelona Clinic Schizophrenia Unit (BCSU), Psychiatry Service, Hospital Clínic de Barcelona, Barcelona, Spain

    M Bernardo

  5. Department Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain

    M Bernardo

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  1. S Mas
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Correspondence to A Lafuente.

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Mas, S., Gassó, P., Boloc, D. et al. Network analysis of gene expression in mice provides new evidence of involvement of the mTOR pathway in antipsychotic-induced extrapyramidal symptoms. Pharmacogenomics J 16, 293–300 (2016). https://doi.org/10.1038/tpj.2015.48

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