Interacting effects of the MAM model of schizophrenia and antipsychotic treatment: Untargeted proteomics approach in adipose tissue
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
33152383
DOI
10.1016/j.pnpbp.2020.110165
PII: S0278-5846(20)30481-4
Knihovny.cz E-resources
- Keywords
- Adipose tissue, Animal model, Antipsychotics, Methylazoxymethanol, Proteomics, Schizophrenia,
- MeSH
- Antipsychotic Agents therapeutic use MeSH
- Haloperidol pharmacology therapeutic use MeSH
- Rats MeSH
- Methylazoxymethanol Acetate pharmacology MeSH
- Disease Models, Animal MeSH
- Intra-Abdominal Fat drug effects embryology metabolism MeSH
- Olanzapine pharmacology therapeutic use MeSH
- Rats, Sprague-Dawley MeSH
- Proteomics MeSH
- Risperidone pharmacology therapeutic use MeSH
- Schizophrenia drug therapy MeSH
- Signal Transduction drug effects MeSH
- Pregnancy MeSH
- TOR Serine-Threonine Kinases metabolism MeSH
- Adipose Tissue drug effects metabolism MeSH
- Prenatal Exposure Delayed Effects chemically induced metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antipsychotic Agents MeSH
- Haloperidol MeSH
- Methylazoxymethanol Acetate MeSH
- mTOR protein, rat MeSH Browser
- Olanzapine MeSH
- Risperidone MeSH
- TOR Serine-Threonine Kinases MeSH
Schizophrenia is a severe neuropsychiatric disease associated with substantially higher mortality. Reduced life expectancy in schizophrenia relates to an increased prevalence of metabolic disturbance, and antipsychotic medication is a major contributor. Molecular mechanisms underlying adverse metabolic effects of antipsychotics are not fully understood; however, adipose tissue homeostasis deregulation appears to be a critical factor. We employed mass spectrometry-based untargeted proteomics to assess the effect of chronic olanzapine, risperidone, and haloperidol treatment in visceral adipose tissue of prenatally methylazoxymethanol (MAM) acetate exposed rats, a well-validated neurodevelopmental animal model of schizophrenia. Bioinformatics analysis of differentially expressed proteins was performed to highlight the pathways affected by MAM and the antipsychotics treatment. MAM model was associated with the deregulation of the TOR (target of rapamycin) signalling pathway. Notably, alterations in protein expression triggered by antipsychotics were observed only in schizophrenia-like MAM animals where we revealed hundreds of affected proteins according to our two-fold threshold, but not in control animals. Treatments with all antipsychotics in MAM rats resulted in the downregulation of mRNA processing and splicing, while drug-specific effects included among others upregulation of insulin resistance (olanzapine), upregulation of fatty acid metabolism (risperidone), and upregulation of nucleic acid metabolism (haloperidol). Our data indicate that deregulation of several energetic and metabolic pathways in adipose tissue is associated with APs administration and is prominent in MAM schizophrenia-like model but not in control animals.
Department of Pathological Physiology Faculty of Medicine Masaryk University Brno Czech Republic
Department of Pharmacology Faculty of Medicine Masaryk University Brno Czech Republic
References provided by Crossref.org
Prenatal MAM exposure raises kynurenic acid levels in the prefrontal cortex of adult rats
The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology
