title: Network analysis of gene expression in mice provides new evidence of involvement of the mTOR pathway in antipsychotic-induced extrapyramidal symptoms.
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.
authors.affiliation: Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Mas
authors.affiliation: Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Gassó
authors.affiliation: Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Boloc
authors.affiliation: Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Rodriguez
authors.affiliation: Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Mármol
authors.affiliation: Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Sánchez
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.|Barcelona Clinic Schizophrenia Unit (BCSU), Psychiatry Service, Hospital Clínic de Barcelona, Barcelona, Spain.|Department Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Bernardo
authors.affiliation: Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Lafuente
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D001522:Behavior, Animal; D015153:Blotting, Western; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009043:Motor Activity; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D038601:Ribosomal Protein S6 / Q000378:metabolism; D018967:Risperidone; D015398:Signal Transduction; D049490:Systems Biology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D038601:Ribosomal Protein S6; C448579:ribosomal protein S6, mouse; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D018967:Risperidone