Abstract

Background: There is barely any evidence of antipsychotic drugs affecting the molecular clockwork in human, yet it is suggested that clock genes are associated with dopaminergic transmission, i.e. the main target of this therapeutics. We decided to verify if haloperidol and olanzapine affect expression of CLOCK, BMAL1, PER1 and CRY1 in a human central nervous system cell line model. Methods: U-87MG human glioblastoma cell line was used as an experimental model. The cells were incubated with or without haloperidol and olanzapine in the concentration of 5 and 20 μM for 24 h. Real-time quantitative polymerase chain reaction with the ΔCT analysis was used to examine the effect of haloperidol and olanzapine on the mRNA expression of the genes. Results: At 5 μM, haloperidol decreased expression of CRY1 almost 20-fold. There was nearly a 1.5-fold increase in expression of PER1. Considering the 20 μM haloperidol concentration and both olanzapine concentrations, no other statistically significant effect was observed. Conclusions: At certain concentration, haloperidol seems to affect expression of particular clock genes in a human central nervous system cell line model, yet mechanism underlying this phenomenon remains elusive.

Highlights

  • There is barely any evidence of antipsychotic drugs affecting the molecular clockwork in human, yet it is suggested that clock genes are associated with dopaminergic transmission, i.e. the main target of this therapeutics

  • No statistically significant differences were found between the viability of the cells treated with the tested antipsychotic drugs (APDs) at a concentration of 5 μM and the relevant control

  • Our findings suggest that haloperidol may affect expression of CRY1 and PER1

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Summary

Introduction

There is barely any evidence of antipsychotic drugs affecting the molecular clockwork in human, yet it is suggested that clock genes are associated with dopaminergic transmission, i.e. the main target of this therapeutics. We decided to verify if haloperidol and olanzapine affect expression of CLOCK, BMAL1, PER1 and CRY1 in a human central nervous system cell line model. Conclusions: At certain concentration, haloperidol seems to affect expression of particular clock genes in a human central nervous system cell line model, yet mechanism underlying this phenomenon remains elusive. The main component of the clock gene network is a cell-autonomous and auto-regulatory transcription–translation feedback loop. It comprises heterodimer CLOCK:BMAL1 (circadian locomotor output cycles kaput, brain and muscle ARNTL-like protein 1, respectively). It is a transcriptional complex enhancing Period (PER) and Cryptochrome (CRY) transcription. PER and CRY proteins accumulate during the day and inhibit their own expression by interaction with CLOCK and BMAL1 back in the cell nucleus (Gustafson & Partch 2015)

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