Network analysis of gene expression in mice provides new evidence of involvement of the mTOR pathway in antipsychotic-induced extrapyramidal symptoms.
Identifieur interne : 000A59 ( Main/Exploration ); précédent : 000A58; suivant : 000A60Network analysis of gene expression in mice provides new evidence of involvement of the mTOR pathway in antipsychotic-induced extrapyramidal symptoms.
Auteurs : S. Mas [Espagne] ; P. Gass [Espagne] ; D. Boloc [Espagne] ; N. Rodriguez [Espagne] ; F. Mármol [Espagne] ; J. Sánchez [Espagne] ; M. Bernardo [Espagne] ; A. Lafuente [Espagne]Source :
- The pharmacogenomics journal [ 1473-1150 ] ; 2016.
Descripteurs français
- KwdFr :
- Activité motrice (MeSH), Affections des ganglions de la base (enzymologie), Affections des ganglions de la base (génétique), Affections des ganglions de la base (induit chimiquement), Affections des ganglions de la base (physiopathologie), Analyse de profil d'expression de gènes (méthodes), Animaux (MeSH), Biologie des systèmes (MeSH), Cartographie d'interactions entre protéines (MeSH), Comportement animal (MeSH), Modèles animaux de maladie humaine (MeSH), Mâle (MeSH), Neuroleptiques (MeSH), Phosphorylation (MeSH), Protéine ribosomique S6 (métabolisme), Prédisposition génétique à une maladie (MeSH), Rispéridone (MeSH), Réseaux de régulation génique (MeSH), Souris (MeSH), Souris de lignée DBA (MeSH), Sérine-thréonine kinases TOR (génétique), Sérine-thréonine kinases TOR (métabolisme), Technique de Western (MeSH), Transduction du signal (MeSH).
- MESH :
- enzymologie : Affections des ganglions de la base.
- génétique : Affections des ganglions de la base, Sérine-thréonine kinases TOR.
- induit chimiquement : Affections des ganglions de la base.
- métabolisme : Protéine ribosomique S6, Sérine-thréonine kinases TOR.
- méthodes : Analyse de profil d'expression de gènes.
- physiopathologie : Affections des ganglions de la base.
- Activité motrice, Animaux, Biologie des systèmes, Cartographie d'interactions entre protéines, Comportement animal, Modèles animaux de maladie humaine, Mâle, Neuroleptiques, Phosphorylation, Prédisposition génétique à une maladie, Rispéridone, Réseaux de régulation génique, Souris, Souris de lignée DBA, Technique de Western, Transduction du signal.
English descriptors
- KwdEn :
- Animals (MeSH), Antipsychotic Agents (MeSH), Basal Ganglia Diseases (chemically induced), Basal Ganglia Diseases (enzymology), Basal Ganglia Diseases (genetics), Basal Ganglia Diseases (physiopathology), Behavior, Animal (MeSH), Blotting, Western (MeSH), Disease Models, Animal (MeSH), Gene Expression Profiling (methods), Gene Regulatory Networks (MeSH), Genetic Predisposition to Disease (MeSH), Male (MeSH), Mice (MeSH), Mice, Inbred DBA (MeSH), Motor Activity (MeSH), Phosphorylation (MeSH), Protein Interaction Mapping (MeSH), Ribosomal Protein S6 (metabolism), Risperidone (MeSH), Signal Transduction (MeSH), Systems Biology (MeSH), TOR Serine-Threonine Kinases (genetics), TOR Serine-Threonine Kinases (metabolism).
- MESH :
- chemical , genetics : TOR Serine-Threonine Kinases.
- chemical , metabolism : Ribosomal Protein S6, TOR Serine-Threonine Kinases.
- chemical : Antipsychotic Agents, Risperidone.
- chemically induced : Basal Ganglia Diseases.
- enzymology : Basal Ganglia Diseases.
- genetics : Basal Ganglia Diseases.
- methods : Gene Expression Profiling.
- physiopathology : Basal Ganglia Diseases.
- Animals, Behavior, Animal, Blotting, Western, Disease Models, Animal, Gene Regulatory Networks, Genetic Predisposition to Disease, Male, Mice, Mice, Inbred DBA, Motor Activity, Phosphorylation, Protein Interaction Mapping, Signal Transduction, Systems Biology.
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.
DOI: 10.1038/tpj.2015.48
PubMed: 26122020
Affiliations:
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Le document en format XML
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Boloc</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Rodriguez, N" sort="Rodriguez, N" uniqKey="Rodriguez N" first="N" last="Rodriguez">N. 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Bernardo</name><affiliation wicri:level="3"><nlm:affiliation>Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Barcelona Clinic Schizophrenia Unit (BCSU), Psychiatry Service, Hospital Clínic de Barcelona, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Barcelona Clinic Schizophrenia Unit (BCSU), Psychiatry Service, Hospital Clínic de Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Department Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Lafuente, A" sort="Lafuente, A" uniqKey="Lafuente A" first="A" last="Lafuente">A. Lafuente</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26122020</idno><idno type="pmid">26122020</idno><idno type="doi">10.1038/tpj.2015.48</idno><idno type="wicri:Area/Main/Corpus">000C33</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000C33</idno><idno type="wicri:Area/Main/Curation">000C33</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000C33</idno><idno type="wicri:Area/Main/Exploration">000C33</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Network analysis of gene expression in mice provides new evidence of involvement of the mTOR pathway in antipsychotic-induced extrapyramidal symptoms.</title><author><name sortKey="Mas, S" sort="Mas, S" uniqKey="Mas S" first="S" last="Mas">S. Mas</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName></affiliation></author><author><name sortKey="Gass, P" sort="Gass, P" uniqKey="Gass P" first="P" last="Gass">P. Gass</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName></affiliation></author><author><name sortKey="Boloc, D" sort="Boloc, D" uniqKey="Boloc D" first="D" last="Boloc">D. Boloc</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Rodriguez, N" sort="Rodriguez, N" uniqKey="Rodriguez N" first="N" last="Rodriguez">N. Rodriguez</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Marmol, F" sort="Marmol, F" uniqKey="Marmol F" first="F" last="Mármol">F. Mármol</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Sanchez, J" sort="Sanchez, J" uniqKey="Sanchez J" first="J" last="Sánchez">J. Sánchez</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Bernardo, M" sort="Bernardo, M" uniqKey="Bernardo M" first="M" last="Bernardo">M. Bernardo</name><affiliation wicri:level="3"><nlm:affiliation>Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Barcelona Clinic Schizophrenia Unit (BCSU), Psychiatry Service, Hospital Clínic de Barcelona, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Barcelona Clinic Schizophrenia Unit (BCSU), Psychiatry Service, Hospital Clínic de Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Department Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Lafuente, A" sort="Lafuente, A" uniqKey="Lafuente A" first="A" last="Lafuente">A. Lafuente</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName></affiliation></author></analytic><series><title level="j">The pharmacogenomics journal</title><idno type="eISSN">1473-1150</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Antipsychotic Agents (MeSH)</term><term>Basal Ganglia Diseases (chemically induced)</term><term>Basal Ganglia Diseases (enzymology)</term><term>Basal Ganglia Diseases (genetics)</term><term>Basal Ganglia Diseases (physiopathology)</term><term>Behavior, Animal (MeSH)</term><term>Blotting, Western (MeSH)</term><term>Disease Models, Animal (MeSH)</term><term>Gene Expression Profiling (methods)</term><term>Gene Regulatory Networks (MeSH)</term><term>Genetic Predisposition to Disease (MeSH)</term><term>Male (MeSH)</term><term>Mice (MeSH)</term><term>Mice, Inbred DBA (MeSH)</term><term>Motor Activity (MeSH)</term><term>Phosphorylation (MeSH)</term><term>Protein Interaction Mapping (MeSH)</term><term>Ribosomal Protein S6 (metabolism)</term><term>Risperidone (MeSH)</term><term>Signal Transduction (MeSH)</term><term>Systems Biology (MeSH)</term><term>TOR Serine-Threonine Kinases (genetics)</term><term>TOR Serine-Threonine Kinases (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activité motrice (MeSH)</term><term>Affections des ganglions de la base (enzymologie)</term><term>Affections des ganglions de la base (génétique)</term><term>Affections des ganglions de la base (induit chimiquement)</term><term>Affections des ganglions de la base (physiopathologie)</term><term>Analyse de profil d'expression de gènes (méthodes)</term><term>Animaux (MeSH)</term><term>Biologie des systèmes (MeSH)</term><term>Cartographie d'interactions entre protéines (MeSH)</term><term>Comportement animal (MeSH)</term><term>Modèles animaux de maladie humaine (MeSH)</term><term>Mâle (MeSH)</term><term>Neuroleptiques (MeSH)</term><term>Phosphorylation (MeSH)</term><term>Protéine ribosomique S6 (métabolisme)</term><term>Prédisposition génétique à une maladie (MeSH)</term><term>Rispéridone (MeSH)</term><term>Réseaux de régulation génique (MeSH)</term><term>Souris (MeSH)</term><term>Souris de lignée DBA (MeSH)</term><term>Sérine-thréonine kinases TOR (génétique)</term><term>Sérine-thréonine kinases TOR (métabolisme)</term><term>Technique de Western (MeSH)</term><term>Transduction du signal (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Ribosomal Protein S6</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Antipsychotic Agents</term><term>Risperidone</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Basal Ganglia Diseases</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Affections des ganglions de la base</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Basal Ganglia Diseases</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Basal Ganglia Diseases</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Affections des ganglions de la base</term><term>Sérine-thréonine kinases TOR</term></keywords><keywords scheme="MESH" qualifier="induit chimiquement" xml:lang="fr"><term>Affections des ganglions de la base</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Gene Expression Profiling</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protéine ribosomique S6</term><term>Sérine-thréonine kinases TOR</term></keywords><keywords scheme="MESH" qualifier="méthodes" xml:lang="fr"><term>Analyse de profil d'expression de gènes</term></keywords><keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr"><term>Affections des ganglions de la base</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Basal Ganglia Diseases</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Behavior, Animal</term><term>Blotting, Western</term><term>Disease Models, Animal</term><term>Gene Regulatory Networks</term><term>Genetic Predisposition to Disease</term><term>Male</term><term>Mice</term><term>Mice, Inbred DBA</term><term>Motor Activity</term><term>Phosphorylation</term><term>Protein Interaction Mapping</term><term>Signal Transduction</term><term>Systems Biology</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Activité motrice</term><term>Animaux</term><term>Biologie des systèmes</term><term>Cartographie d'interactions entre protéines</term><term>Comportement animal</term><term>Modèles animaux de maladie humaine</term><term>Mâle</term><term>Neuroleptiques</term><term>Phosphorylation</term><term>Prédisposition génétique à une maladie</term><term>Rispéridone</term><term>Réseaux de régulation génique</term><term>Souris</term><term>Souris de lignée DBA</term><term>Technique de Western</term><term>Transduction du signal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26122020</PMID><DateCompleted><Year>2017</Year><Month>03</Month><Day>09</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1473-1150</ISSN><JournalIssue CitedMedium="Internet"><Volume>16</Volume><Issue>3</Issue><PubDate><Year>2016</Year><Month>06</Month></PubDate></JournalIssue><Title>The pharmacogenomics journal</Title><ISOAbbreviation>Pharmacogenomics J</ISOAbbreviation></Journal><ArticleTitle>Network analysis of gene expression in mice provides new evidence of involvement of the mTOR pathway in antipsychotic-induced extrapyramidal symptoms.</ArticleTitle><Pagination><MedlinePgn>293-300</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/tpj.2015.48</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Mas</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gassó</LastName><ForeName>P</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Boloc</LastName><ForeName>D</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rodriguez</LastName><ForeName>N</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mármol</LastName><ForeName>F</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sánchez</LastName><ForeName>J</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bernardo</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Barcelona Clinic Schizophrenia Unit (BCSU), Psychiatry Service, Hospital Clínic de Barcelona, Barcelona, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lafuente</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>06</Month><Day>30</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Pharmacogenomics J</MedlineTA><NlmUniqueID>101083949</NlmUniqueID><ISSNLinking>1470-269X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014150">Antipsychotic Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D038601">Ribosomal Protein S6</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C448579">ribosomal protein S6, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="C546843">mTOR protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>L6UH7ZF8HC</RegistryNumber><NameOfSubstance UI="D018967">Risperidone</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014150" MajorTopicYN="Y">Antipsychotic Agents</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001480" MajorTopicYN="N">Basal Ganglia Diseases</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="N">chemically induced</QualifierName><QualifierName UI="Q000201" MajorTopicYN="N">enzymology</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001522" MajorTopicYN="N">Behavior, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015153" MajorTopicYN="N">Blotting, Western</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020869" MajorTopicYN="Y">Gene Expression Profiling</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053263" MajorTopicYN="Y">Gene Regulatory Networks</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020022" MajorTopicYN="N">Genetic Predisposition to Disease</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008811" MajorTopicYN="N">Mice, Inbred DBA</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009043" MajorTopicYN="N">Motor Activity</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010766" MajorTopicYN="N">Phosphorylation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D025941" MajorTopicYN="N">Protein Interaction Mapping</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D038601" MajorTopicYN="N">Ribosomal Protein S6</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018967" MajorTopicYN="Y">Risperidone</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D049490" MajorTopicYN="N">Systems Biology</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000378" 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IdType="pubmed">19454602</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed><affiliations><list><country><li>Espagne</li></country><region><li>Catalogne</li><li>Communauté de Madrid</li></region><settlement><li>Barcelone</li><li>Madrid</li></settlement></list><tree><country name="Espagne"><region name="Catalogne"><name sortKey="Mas, S" sort="Mas, S" uniqKey="Mas S" first="S" last="Mas">S. Mas</name></region><name sortKey="Bernardo, M" sort="Bernardo, M" uniqKey="Bernardo M" first="M" last="Bernardo">M. Bernardo</name><name sortKey="Bernardo, M" sort="Bernardo, M" uniqKey="Bernardo M" first="M" last="Bernardo">M. Bernardo</name><name sortKey="Bernardo, M" sort="Bernardo, M" uniqKey="Bernardo M" first="M" last="Bernardo">M. Bernardo</name><name sortKey="Bernardo, M" sort="Bernardo, M" uniqKey="Bernardo M" first="M" last="Bernardo">M. Bernardo</name><name sortKey="Boloc, D" sort="Boloc, D" uniqKey="Boloc D" first="D" last="Boloc">D. Boloc</name><name sortKey="Gass, P" sort="Gass, P" uniqKey="Gass P" first="P" last="Gass">P. Gass</name><name sortKey="Gass, P" sort="Gass, P" uniqKey="Gass P" first="P" last="Gass">P. Gass</name><name sortKey="Gass, P" sort="Gass, P" uniqKey="Gass P" first="P" last="Gass">P. Gass</name><name sortKey="Lafuente, A" sort="Lafuente, A" uniqKey="Lafuente A" first="A" last="Lafuente">A. Lafuente</name><name sortKey="Lafuente, A" sort="Lafuente, A" uniqKey="Lafuente A" first="A" last="Lafuente">A. Lafuente</name><name sortKey="Lafuente, A" sort="Lafuente, A" uniqKey="Lafuente A" first="A" last="Lafuente">A. Lafuente</name><name sortKey="Marmol, F" sort="Marmol, F" uniqKey="Marmol F" first="F" last="Mármol">F. Mármol</name><name sortKey="Mas, S" sort="Mas, S" uniqKey="Mas S" first="S" last="Mas">S. Mas</name><name sortKey="Mas, S" sort="Mas, S" uniqKey="Mas S" first="S" last="Mas">S. Mas</name><name sortKey="Rodriguez, N" sort="Rodriguez, N" uniqKey="Rodriguez N" first="N" last="Rodriguez">N. Rodriguez</name><name sortKey="Sanchez, J" sort="Sanchez, J" uniqKey="Sanchez J" first="J" last="Sánchez">J. Sánchez</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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