PMID- 26122020
OWN - NLM
STAT- MEDLINE
DCOM- 20170309
LR  - 20211204
IS  - 1473-1150 (Electronic)
IS  - 1470-269X (Linking)
VI  - 16
IP  - 3
DP  - 2016 Jun
TI  - Network analysis of gene expression in mice provides new evidence of involvement 
      of the mTOR pathway in antipsychotic-induced extrapyramidal symptoms.
PG  - 293-300
LID - 10.1038/tpj.2015.48 [doi]
AB  - 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.
FAU - Mas, S
AU  - Mas S
AD  - Department of Pathological Anatomy, Pharmacology and Microbiology, University of 
      Barcelona, Barcelona, Spain.
AD  - Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, 
      Spain.
AD  - Centro de Investigacion Biomedica en Red de Salud Mental (CIBERSAM), Madrid, 
      Spain.
FAU - Gasso, P
AU  - Gasso P
AD  - Department of Pathological Anatomy, Pharmacology and Microbiology, University of 
      Barcelona, Barcelona, Spain.
AD  - Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, 
      Spain.
AD  - Centro de Investigacion Biomedica en Red de Salud Mental (CIBERSAM), Madrid, 
      Spain.
FAU - Boloc, D
AU  - Boloc D
AD  - Department of Pathological Anatomy, Pharmacology and Microbiology, University of 
      Barcelona, Barcelona, Spain.
FAU - Rodriguez, N
AU  - Rodriguez N
AD  - Department of Pathological Anatomy, Pharmacology and Microbiology, University of 
      Barcelona, Barcelona, Spain.
FAU - Marmol, F
AU  - Marmol F
AD  - Department of Pathological Anatomy, Pharmacology and Microbiology, University of 
      Barcelona, Barcelona, Spain.
FAU - Sanchez, J
AU  - Sanchez J
AD  - Department of Pathological Anatomy, Pharmacology and Microbiology, University of 
      Barcelona, Barcelona, Spain.
FAU - Bernardo, M
AU  - Bernardo M
AD  - Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, 
      Spain.
AD  - Centro de Investigacion Biomedica en Red de Salud Mental (CIBERSAM), Madrid, 
      Spain.
AD  - Barcelona Clinic Schizophrenia Unit (BCSU), Psychiatry Service, Hospital Clinic 
      de Barcelona, Barcelona, Spain.
AD  - Department Psychiatry and Clinical Psychobiology, University of Barcelona, 
      Barcelona, Spain.
FAU - Lafuente, A
AU  - Lafuente A
AD  - Department of Pathological Anatomy, Pharmacology and Microbiology, University of 
      Barcelona, Barcelona, Spain.
AD  - Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, 
      Spain.
AD  - Centro de Investigacion Biomedica en Red de Salud Mental (CIBERSAM), Madrid, 
      Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150630
PL  - United States
TA  - Pharmacogenomics J
JT  - The pharmacogenomics journal
JID - 101083949
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Ribosomal Protein S6)
RN  - 0 (ribosomal protein S6, mouse)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - L6UH7ZF8HC (Risperidone)
SB  - IM
MH  - Animals
MH  - *Antipsychotic Agents
MH  - Basal Ganglia Diseases/chemically induced/enzymology/*genetics/physiopathology
MH  - Behavior, Animal
MH  - Blotting, Western
MH  - Disease Models, Animal
MH  - *Gene Expression Profiling/methods
MH  - *Gene Regulatory Networks
MH  - Genetic Predisposition to Disease
MH  - Male
MH  - Mice
MH  - Mice, Inbred DBA
MH  - Motor Activity
MH  - Phosphorylation
MH  - Protein Interaction Mapping
MH  - Ribosomal Protein S6/metabolism
MH  - *Risperidone
MH  - Signal Transduction
MH  - Systems Biology
MH  - TOR Serine-Threonine Kinases/*genetics/metabolism
EDAT- 2015/07/01 06:00
MHDA- 2017/03/10 06:00
CRDT- 2015/07/01 06:00
PHST- 2014/12/23 00:00 [received]
PHST- 2015/04/10 00:00 [revised]
PHST- 2015/05/18 00:00 [accepted]
PHST- 2015/07/01 06:00 [entrez]
PHST- 2015/07/01 06:00 [pubmed]
PHST- 2017/03/10 06:00 [medline]
AID - tpj201548 [pii]
AID - 10.1038/tpj.2015.48 [doi]
PST - ppublish
SO  - Pharmacogenomics J. 2016 Jun;16(3):293-300. doi: 10.1038/tpj.2015.48. Epub 2015 
      Jun 30.