MicroRNA Plasma Levels Before And After Antipsychotic Treatment For Male Patients With Schizophrenia

As a type of eukaryotic endogenous RNA, microRNAs (miRNAs) are non-codingand single-stranded, regulating the gene expression by combining with certainmRNAs or by controlling the gene translation process of mRNA targets, thereforeparticipate in the occurrence and development process of various diseases. MiRNAsexist widely in blood plasma and serum, while their types and amounts change withthe physical condition and disease. The circulating miRNAs are sufficiently stabledue to their good resistance to degradation. It is assumed that at least1/3of theknown miRNAs express specifically in brain. According to literatures, the expressionof miRNAs in postmortem brain tissues with schizophrenia differs significantly fromthe ones in normal postmortem brain tissues. Profiting from the recent studies,miRNAs are known as the potential therapeutic targets of psychotropic drugs.Literatures have reviewed that the expression level of some miRNAs changes withthe effect of psychotropic drugs. As miRNA can suppress the translation of proteinthrough matching with the non-completely-complemented mRNAs, a single miRNAmay have various target genes, and a single gene may be regulated by variousmiRNAs. Due to such complicated regulating network, miRNAs are able to targethundreds of genes that may be involved in the varied aspects of the disease process,thus become the unifying link between the diverse findings observed in schizophrenia,for example structural developmental anomalies, neurotransmitter alterations andresponse to treatment. Through literature review, this thesis screens out5schizophrenia-related miRNAs which are expressed specifically in brain and releasedinto blood, namely miR-181b, miR-24, miR-199a-3p, miR-106b and miR-26b. By means of the quantitative analysis with real-time PCR (RT-PCR), this thesis studiesthe microRNA plasma levels before and after antipsychotic treatment for malepatients with schizophrenia.Objective:To investigate the plasma levels of miR-181b, miR-24, miR-199a-3p, miR-106b andmiR-26b before and after antipsychotic treatment for male patients withschizophrenia, in addition with the influence of different antipsychotics on the changeof expression levels of different miRNAs.Method:The plasma of40male adult patients with schizophrenia and40male adultindividuals were collected. The plasma miR-181b, miR-24, miR-199a-3p, miR-106band miR-26b levels of both the patient group (drug-free,2-week medicated, and4-week medicated) and the control group were measured with RT-PCR.Result:1. The plasma level microRNA in the patients differed significantly from the controlgroup before treatment. MiR-181b, miR-106b and miR-24increased significantlywhile miR-199a-3p and miR26b decreased significantly (both p<0.001).2. The patients’ conditions improved with the antipsychotics treatment, while thePANSS score decreased gradually. The plasma miR-181b and miR-106b levelsdecreased and the plasma miR-26b level increased. The plasma miR-181b level of thepatients after2and4week medicated were compared with the ones before treatment(P<0.001). The plasma miR-106b and miR-26b levels of the patients after4-weekmedicated were compared with the ones before treatment (P<0.001).3. Statistic difference has not been observed in the downregulation in the patientgroup of plasma miR-181b and miR-106b levels as well as in the upregulation ofmiR-26level after the treatment with risperidone, olanzapine and clozapine (P>0.05). 4. The plasma miR-26b levels of the male patients with family histories of mentalillness were significantly higher than the ones without them (P<0.001).Conclusion：1. It is possible for miR-181, miR-24, miR-199a-3p, miR-106b and miR-26b to takepart in the pathogenesis of schizophrenia in male patients.2. The plasma miR-181b, miR-106b and miR-26b levels in male schizophreniapatients are affected by antipsychotics.3. For male schizophrenia patients, there is no statistic difference in the regulation ofplasma miR-181b, miR-106b and miR-26b levels by risperidone, olanzapine andclozapine.4. The plasma miR-26b levels are closely related to the fact that if the patient has afamily history of mental illness. Mir-26b may also participate in the process thathereditary factors affect schizophrenia pathogenesis.