Abstract
BackgroundThe 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.ResultsHaloperidol treatment (0.2 μM) 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 μM) responded with a five-fold and three-fold increase in QKI-7, 6 and 24 hours after treatment, respectively (p-values < 0.0001).ConclusionThe 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.
Highlights
The quaking homolog, KH domain RNA binding (QKI) is a candidate gene for schizophrenia
The results in astrocytoma cell line (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
A slight decrease in mRNA expression was detected for QKI-7 when the U343 cell line was treated with Risperidone or Clozapine (Figure 1C and Additional file 1, Table 2a)
Summary
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. Messenger RNA expression levels of splice variants QKI-5, QKI-6 and QKI-7 were measured by Real-Time PCR. QKI was recently proposed as a candidate gene for schizophrenia based on linkage, association and mRNA expression studies [1,2,3]. The alteration of expression levels involves differential expression of splice variants. An earlier study showed decreased expression levels of QKI splice variant seven (QKI-7) in frontal cortex of schizophrenia patients [2]. QKI expression was recently shown to be both necessary and sufficient to promote myelination of oligodendrocytes [6]. Astrocytes play a role in myelination by mediating communication between axons and myelinating glial cells [7] and it has been suggested that these two cell types are involved in the pathophysiology of schizophrenia. [8]
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