Study On Schizophrenia Associated With Maternal - Induced Schizophrenia

Section1. Association study of schizophrenia in Chinese HanSingle nucleotide polymorphisms (SNPs) in3’untranslated regions (3’-UTRs) of genes may affect miRNA binding to messenger RNA and contribute to the risk of disease. miRNA play important role in progress of schizophrenia, whether the SNPs that modify miRNA binding in the3’-UTR are involved in schizophrenia-related genes remains unclear. It is necessary to explore the association of these SNPs in schizophrenia.Using bioinformatics methods, we selected803SNPs from the3’-UTRs of425candidate genes for schizophrenia. The potential target SNPs were recognized by Gibbs free energy of miRNA binding using miRanda, microinspector, PicTar and RNAhybrid. Some SNPs were associated in the literature with schizophrenia or other related neurological diseases. A case-control study of nine SNPs not previously reported as significant in any disease was carried out in a Chinese-Han cohort. We found that rs3219151(C＞T, GABRA6) showed significant decreased risk for schizophrenia (OR=0.8121, P=0.008, P adjust=0.03).Our results suggest that rs3219151of GABRA6was associated significantly to decrease the risk of schizophrenia. Section2. Prenatal famine reprogramed postnatal gene expression in mammal’s brainEpidemiological studies have identified prenatal exposure to famine as a risk factor for schizophrenia, and animal models of prenatal malnutrition displayed structural and functional brain abnormalities implicated in schizophrenia. To investigate the molecular mechanism that leads to an increasing risk for schizophrenia due to prenatal exposure to famine, we first carried out expression profiling screens for genes respond to prenatal nutrition conditions in the prefrontal cortex (PFC) and hippocampus of rats. Offspring of the famine model RLP50exhibited differences in neurotransmitters and olfactory associated genes expression relative to those of the normal group in PFC, suggesting abnormalities in cortical patterning. In the hippocampus, the differentially expressed genes were enriched in the gene ontology categories related to synaptic function and transcription regulation. DNA methylome profiling of the offspring’s hippocampus revealed a systematic epigenetic reprogramming of which majority changes appeared to be hypermethylation (86.9%) due to prenatal nutritional deficiencies. Remarkably, the functional enrichment of several gene ontology categories was identified in both profiling screens, including plasma membrane (P=2.37×10-9in gene expression, and P=5.36×10-9in DNA methylome). Furthermore, Mecp2and Slc2al, two genes associated with cognitive impairment, showed significant down-regulation and changes in cytosine methylation in the hippocampus of the RLP50offspring.Collectively, our results indicate that prenatal exposure to famine leads to the reprogramming of postnatal brain gene expression, which reduces the transcription activity of many genes. The process may impair learning and memory ability and contribute to a predisposition to schizophrenia.