Abstract

In the present investigation antipsychotic drug-induced miRNA modulations in glial cells were analyzed through miRNA expression in antipsychotic drugs-treated C6 cells using a miRNA microarray. Seventeen miRNAs were upregulated by haloperidol and 10 miRNAs were upregulated by risperidone in C6 cells. Thirty-six miRNAs were downregulated by clozapine in C6 cells. Six miRNAs (rno-let-7a-5p, rno-miR-221-3p, rno-miR-152-3p, rno-miR-345-5p, rno-miR-3473 and rno-miR-551b-5p) were selected for validation by reverse transcription-quantitative polymerase chain reaction, the results of which showed almost the same expression trends as the microarray results. mRNA and protein expression of potential targets for some validated miRNAs was examined using reverse transcription-quantitative polymerase chain reaction, western blot analysis and immunofluorescence staining. Reduction of miRNA (rno-let-7a-5p, rno-miR-152-3p and rno-miR-221-3p) caused by clozapine treatment could further induce expressions of predicted target genes/proteins (atg12, cdkn1b, c-myc and K-ras) in C6 cells. miRNAs regulation induced by haloperidol or risperidone were not closely related to predicted target genes/proteins expressions. It was concluded that the regulatory trends between antipsychotic drug-induced miRNA and the mRNA/protein expression of potential targets of the examined miRNAs were not quite the same. Clozapine, but not haloperidol or risperidone, could modulate miRNA expression to further regulate protein expression in C6 cells.