TY - JOUR
TI - A longitudinal study of alterations of circulating DJ-1 and miR203a-3p in association to olanzapine medication in a sample of first episode patients with schizophrenia
AU - Tsoporis, J.N.
AU - Ektesabi, A.M.
AU - Gupta, S.
AU - Izhar, S.
AU - Salpeas, V.
AU - Rizos, I.K.
AU - Kympouropoulos, S.P.
AU - dos Santos, C.C.
AU - Parker, T.G.
AU - Rizos, E.
JO - Journal of Psychiatric Research
PY - 2022
VL - 146
TODO - null
SP - 109-117
PB - Elsevier Ireland Ltd
SN - 0022-3956
TODO - 10.1016/j.jpsychires.2021.12.049
TODO - hydrogen peroxide;  luciferase;  messenger RNA;  microRNA;  microRNA 203a 3p;  olanzapine;  protein deglycase DJ-1;  unclassified drug, 3' untranslated region;  adult;  Article;  bioinformatics;  clinical article;  controlled study;  down regulation;  exosome;  female;  gene expression regulation;  gene set enrichment analysis;  genetic transfection;  human;  human cell;  human tissue;  longitudinal study;  male;  monotherapy;  mRNA expression level;  oxidative stress;  pathogenesis;  pathophysiology;  Positive and Negative Syndrome Scale;  protein blood level;  protein expression level;  reporter gene;  schizophrenia;  transcription initiation;  umbilical vein endothelial cell;  upregulation;  young adult
TODO - Among different proposed pathophysiological mechanisms, redox imbalance has been suggested to be a potential contributor in the pathogenesis of schizophrenia. DJ-1 is a redox-sensitive protein that has been shown to have neuroprotective function in the brain in Parkinson's disease and other neurodegenerative diseases. However, a role for DJ-1 in schizophrenia is unknown. Bioinformatic analysis suggested that microRNA (miR)-203a-3p could target the 3′ untranslated region (UTR) of DJ-1. In whole blood and blood-derived exosomes of 11 first episode antipsychotic naïve schizophrenia patients, DJ-1 protein and mRNA demonstrated decreased DJ-1 mRNA and protein and increased miR203a-3p levels compared to healthy controls. In whole blood, antipsychotic monotherapy with olanzapine for 6 weeks increased DJ-1 and attenuated miR203a-3p levels, whereas in blood derived exosomes, olanzapine returned DJ-1 and miR203a-3p to levels seen healthy controls. Consistent with this finding, we showed that human umbilical vein endothelial cells (HUVACs) transfected with a DJ-1–3′ UTR luciferase reporter construct displayed reduced gene expression when subjected to the oxidative stressor H2O2. Transfection of a miR203a-3p mimic into HUVACs reduced DJ-1–3 ‘UTR reporter gene expression, while transfection of an anti miR-203a-3p prevented the H2O2-induced downregulation of the reporter gene. We conclude that miR-203a-3p is an essential mediator of oxidative stress in schizophrenia via its ability to target the 3’ UTR of DJ-1 and antipsychotic monotherapy restores DJ-1 antioxidant levels by regulating miR203a-3p expression. miR-203a-3p and DJ-1 might represent attractive targets for the treatment of pathologies such as schizophrenia that has underlying oxidative stress. © 2021 Elsevier Ltd
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