Interacting effects of the MAM model of schizophrenia and antipsychotic treatment: Untargeted proteomics approach in adipose tissue

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2021-06, Vol.108, p.110165, Article 110165
• Main Authors: Kucera, Jan, Horska, Katerina, Hruska, Pavel, Kuruczova, Daniela, Micale, Vincenzo, Ruda-Kucerova, Jana, Bienertova-Vasku, Julie
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Animal model; Animals; Antipsychotic Agents - therapeutic use; Antipsychotics; Disease Models, Animal; Female; Haloperidol - pharmacology; Haloperidol - therapeutic use; Intra-Abdominal Fat - drug effects; Intra-Abdominal Fat - embryology; Intra-Abdominal Fat - metabolism; Methylazoxymethanol; Methylazoxymethanol Acetate - pharmacology; Olanzapine - pharmacology; Olanzapine - therapeutic use; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Prenatal Exposure Delayed Effects - metabolism; Proteomics; Rats; Rats, Sprague-Dawley; Risperidone - pharmacology; Risperidone - therapeutic use; Schizophrenia; Schizophrenia - drug therapy; Signal Transduction - drug effects; TOR Serine-Threonine Kinases - metabolism
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2020.110165

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. •Proteomics show deregulated mTOR in adipose tissue of schizophrenia-like rat model.•Antipsychotics alter adipose proteome in schizophrenia-like rats but not in controls.•Different antipsychotics have a distinct impact on the adipose tissue proteome.•Antipsychotics modify metabolic and energetic pathways in adipose tissue.