| Research background:Schizophrenia is a complex clinical syndrome with multiple manifestations,and the illness always accompanies relapse as well as incurability.The main pathogenesis of schizophrenia is the abnormal transcription of neurotransmitter,which leads to the nervous system diseases.Genetic factors and environmental factors are involved in the pathogenesis of schizophrenia,the interaction between them leads to occurrence of schizophrenia.Environmental factors producing schizophrenia may be caused by epigenetic modifications including DNA methylation and histone acetylation.At present,drug treatment has little effect on cognitive impairment of schizophrenia.It has been found that HDACi can improve learning and memory,synaptic plasticity,gene regulation and the efficacy of antipsychotic drugs.HDACi owning the ability to inhibit deacetylation of HDAC can promote gene expression,improve the imbalance between histone acetylation and histone deacetylation,and promote the expression of nerve growth factors and apoptosis genes.These changes can inhibit the apoptosis and improve neurological deficits,and then play a regulatory role in the cognitive impairment of schizophrenia.Therefore,HDACi is likely to be an important potential therapeutic method to improve cognitive function and dysfunction in schizophrenic.Sodium butyrate belongs to HDACi,which can inhibit the activity of HDAC to induce histone acetylation,but its specific mechanism needs to be verified by a lot of experiments.Research objectives:In this study,we established an animal model of schizophrenia,in order to investigate the gene expression of Bdnf4,Disc1,Dnmt3 a,Grm2,Grm3,Hdac2,Hdac3,Mecp2,RELN in schizophrenia,and to observe working mechanism of sodium butyrate on schizophrenia,then to observe the relationship between ionizing radiation and HDACi.Research methods:The rat model of schizophrenia was established by means of drugs phencyclidine and methinonine.The Morris water maze test was used to evaluate the behavioral changes and cognitive function of rats,in order to verifying the success of animal models.After that,the rats were treated with sodium butyrate,chlorpromazine,or combined medication.Then rats in control group and PMB group received 2Gy dose of ionizing radiation.The expression of m RNA in the four brain regions(prefrontal cortex,amygdala,caudate putamen and hippocampus)of the schizophrenia model was detected by Real Time PCR.SPSS16.0 software was used for statistical analysis.Research results:1.the abnormal change of Hdac2 gene,Hdac3 gene,Grm2 gene,Grm3 gene,Bdnf4 gene and reelin gene resulted in the occurrence of schizophrenia in animal model.2.According to the results of this study,sodium butyrate can reverse the abnormal expression of Dnmt3 a gene,Grm2 gene,Grm3 gene,Hdac2 gene,Hdac3 gene,Reelin gene in schizophrenia animal model.3.The results showed that the expression of m RNA about Bdnf4,Dnmt3 a,Hdac2,Hdac3 gene in four brain regions is enhanced by 2Gy irradiation and the expression of m RNA about Disc1 gene in four brain regions is reduced by 2Gy irradiation.The results show that the Bdnf4,Dnmt3 a,Hdac2,Hdac3 genes are positively correlated with the biological effects of ionizing radiation,and the Disc1 gene is negatively correlated with the biological effects of ionizing radiation.4.Bdnf4 gene,Disc1 gene,Dnmt3 a gene,Hdac2 gene,Hdac3 gene may be related to the biological effects of ionizing radiation.and Ionizing radiation may interact with sodium butyrate in hippocampus which can inhibits the expression of genes.Conclusions:1.Dnmt3 a gene,Grm2 gene,Grm3 gene,Hdac2 gene,Hdac3 gene may be the target genes of HDACi sodium butyrate.2.Sodium butyrate may improve the disorder of cognition in animal model through epigenetic modification,which has a promising prospect.3.Bdnf4 gene,Disc1 gene,Dnmt3 a gene,Hdac2 gene,Hdac3 gene may be related to the biological effects of ionizing radiation.and Ionizing radiation may interact with sodium butyrate in hippocampus which can inhibits the expression of genes. |
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