clozapine and Astrocytoma

The quaking homolog, KH domain RNA binding (mouse) (QKI) is a candidate gene for schizophrenia. Disturbed QKI mRNA expression is observed in the prefrontal cortex of patients, and some of these changes correlate to treatment with antipsychotic drugs.To test if low doses of antipsychotic drugs can modify QKI mRNA expression, human astrocytoma (U343) and oligodendroglioma (HOG) cell lines were treated with five different antipsychotic drugs including Haloperidol, Aripiprazole, Clozapine, Olanzapine and Risperidone. Messenger RNA expression levels of splice variants QKI-5, QKI-6 and QKI-7 were measured by Real-Time PCR.. Haloperidol treatment (0.2 microM) doubled QKI-7 mRNA levels in U343 cells after 6 hours (p-value < 0.02). The effect was dose dependent, and cells treated with ten times higher concentration (2 microM) responded with a five-fold and three-fold increase in QKI-7, 6 and 24 hours after treatment, respectively (p-values < 0.0001).. The results in U343 cells suggest that QKI-7 mRNA expression in human astrocytes is induced by Haloperidol, at concentrations similar to plasma levels relevant to clinical treatment of schizophrenia. The molecular mechanism of action of antipsychotic drugs after binding to receptors is not well known. We hypothesize that QKI regulation is involved in this mechanism.

Topics: Alternative Splicing; Antipsychotic Agents; Aripiprazole; Astrocytoma; Benzodiazepines; Cell Line, Tumor; Clozapine; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Haloperidol; Humans; Olanzapine; Piperazines; Quinolones; Receptors, Dopamine D2; Reverse Transcriptase Polymerase Chain Reaction; Risperidone; RNA-Binding Proteins; RNA, Messenger; Time Factors