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ObjectiveTo study the effects of Wendantang on the expression of miRNA-219， N-methyl-D-aspartate receptor 2B （NR2B）， disrupted in schizophrenia 1 （DISC1）， and Ca2+/calmodulin-dependent protein kinase Ⅱγ （CaMKⅡγ） in the frontal lobe of rats with schizophrenia. MethodSixty rats were randomly divided into six groups， namely normal group， model group， high-， medium-， and low-dose Wendantang groups， and clozapine group， with 10 rats in each group. Rats in high-， medium-， and low-dose Wendantang groups were intragastric with 40， 20， and 10 g·kg-1 Wendantang， and the ones in clozapine group were intragastric with 0.02 g·kg-1 clozapine， those in normal and model group were intragastric with equal volume of normal saline， once a day. After 21 days of administration， rats in all groups except for the normal group were injected with 0.6 mg·kg-1 dizocilpine maleate （MK-801） into the left abdominal cavity for inducing acute schizophrenia. The stereotypic behavior and ataxia in rats were scored according to SAMS and HOFFMAN criteria. The morphological changes in the prefrontal cortex were observed by hematoxylin-eosin （HE） staining. The protein expression levels of NR2B, DISC1 and CaMKⅡγ in the frontal lobe was detected by Western blot. The mRNA expression levels of miRNA-219 was detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. ResultCompared with normal group， the model group exhibited significantly increased stereotypic behavior and ataxia scores （P<0.01）， karyopyknosis and karyolysis in most neurons of the prefrontal cortex， and down-regulated NR2B， DISC1， and CaMKⅡγ protein expression （P<0.01） and miRNA-219， NR2B， DISC1， and CaMKⅡγ mRNA expression （P<0.01）. Compared with model group， Wendantang high-， medium-， and low-doses group lowered the scores of stereotypic behavior and ataxia at 50， 60 mmin（P<0.05，P<0.01）. In high- and medium-dose Wendantang groups， the neurons in the prefrontal cortex were densely arranged. The karyopyknosis and karyolysis were alleviated to varying degrees. The NR2B protein expression in the frontal lobe was up-regulated （P<0.01）. In the medium- and low-dose Wendantang groups， the DISC1 protein expression in the frontal lobe was up-regulated （P<0.05，P<0.01）. Wendantang at each dose significantly increased the CaMKⅡγ protein expression （P<0.05） and miRNA-219， NR2B， DISC1， and CaMKⅡγ mRNA expression in the frontal lobe （P<0.05，P<0.01）. ConclusionWendantang improves the scores of stereotypical behavior and ataxia， relieves the karyopyknosis and karyolysis of neurons in the prefrontal cortex， and increases the expression levels of miRNA-219， NR2B， DISC1， and CaMKⅡγ of rats with schizophrenia， so as to alleviate the schizophrenic-like symptoms and schizophrenia.
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Objective To explore the difference of DISC1 gene polymorphism between schizophrenia patients and normal subjects,as well as the association of gene polymorphism with mRNA expression.methods 40 schizophrenia patients and 40 normal subjects were recruited randomly from southern region of Fujian,China.DISC1 mRNA level was assessed by RT-PCR and the genotype was evaluated by sequencing with the amplified PCR products from peripheral blood DNA.Result srs6675281 locus only found CC type,other types were not found.According to the genotyping Result ,the rs821616 locus has AA,AT and TT three types,but the genotype and allele frequency between the two groups were not significantly different (Genotype:x2=0.923,P=0.63;Allele:A>T,x2=0.656,P=0.418).As far as rs11122319 locus,AA,AG and GG three types were found in this study,there was no significant difference between patients and normal controls (Genotype:x2=3.922,P=0.141;Allele:A>G,x2=0.184,P=0.668).Subjects were divided into AA,AG,GG three types based on rs1417584 locus genotyping,however the genotypes and alleles of this locus between the two groups were significant difference (Genotype:x2=6.631,P=0.042;Allele:A>G,x2=4.592,P=0.032),and the DISC1 mRNA expression that corresponding to the genotype AG in patients and normal subjects was significantly different (t=3.916,P=0.004).Conclusion Based on these findings,rs1417584 locus may be implicated the expression and regulation of DISC1 gene,may be a pathogenic factor of schizophrenia and the genotype AG may be corresponding to a higher risk.
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Objective To investigate the relationship between the single nucleotide polymorphisms(SNPs) of disrupted in schizophrenia 1 (DISC1) gene and autism in Chinese Han children.Methods Genome-wide SNP genotyping was performed by using Illumina HumanHap CNV370-Duo Chip in 278 autistic trios,157 autistic individuals and 435 healthy controls.Genotype data of SNPs within DISC1 gene were selected.The association between these SNPs loci and autism was analyzed through case-control association analysis and family-based transmission disequilibrium test.Results Fifty-two SNPs were involved for further analysis.1.Case-control association analysis showed that 6 SNPs (rs4658939,rs2793093,rs10495309,rs2492367,rs1 1122362,rs1073179) and 7 haplotypes (AGAAAG constructed with rs823163-rs823161-rs4658933-rs1417585-rs10864693-rs6541281,GGG and AAA constructed with rs4658939-rs2793093-rs10495309,GG and AG constructed with rs2492367-rs12046794,GAA constructed with rs9432040-rs2356606-rs1 1122362 and GG constructed with rs9431714-rs1073179) had significant differences between autistic patients and controls(x2 =4.704,4.915,5.568,8.087,4.043,5.183,5.369,5.295,4.440,5.304,7.615,4.018,4.811,P =0.030,0.027,0.018,0.005,0.044,0.023,0.021,0.021,0.035,0.021,0.006,0.045,0.028).2.In the transmission disequilibrium test analysis,2 SNPs (rs4658945,rs11122362) and 2 haplotypes (AG constructed with rs10495310-rs4658945,GAA constructed with rs9432040-rs2356606-rs11122362) showed significant transmission disequilibrium(x2=4.445,5.400,3.973,5.126,P =0.035,0.020,0.046,0.024).Conclusions The polymorphism of rs11122362 and GAA haplotype constructed with rs9432040-rs2356606-rs11122362 are associated with autism,and DISC1 gene is a susceptibility gene for autism in Chinese Han children.
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ObjectiveTo analyze the association between single nucleotide polymorphisms (SNPs) in DISC1 gene.MethodsThe studied sample consisted of 528 patients with schizophrenia (264 males and 264 females) and 528 healthy controls (264 males and 264 females).Two function SNPs were selected and gcnotyped by Illumina Golden Gate assay.Genotype and allele frequencies were compared between patients and controls to assess the association to schizophrenia.The clinical features of the hospital first patients were further examined with the Positive and Negative Syndrome Scale (PANSS) before trcatment with antipsychotics.ResultsTwo SNPs were genotyped in subjects.A significant association was found between rs3737597 and schizophrenia in genotype (387:133:8,350:164:14) and allele frequencies (907:149,864:192,P＜0.05 ).Moreover,the haplotypes,A-A constructed from two SNPs showed significant differences between cases and controls ( P＜ 0.05).For rs821616,there were significant difference in positive syndrome score,delusions and poor rapport between patients with genotypes AA or not.ConclusionThis study describes a positive association between DISC(1) and schizophrenia in the Han Chinese population and DISC1 is the susceptible gene in schiz ophrenia.
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T,P=0.008; Genotype:P=0.031)of DISC1 gene were significantly associated with schizophrenia.The haplotypes constructed by these two markers were significantly associated with schizophrenia,such as AT(?2=7.065,P=0.008,OR=1.42,95%CI=1.10~1.83)and GA(?2=6.009,P=0.014,OR=0.80,95%CI=0.68~0.96).When the subjects examined with the positive and negative syndrome scale(PANSS),the risk haplotype AT was not significantly correlated with positive,negative,excitement,depression and cognitive impairment factors of PANSS. Conclusion:These findings provide further evidence for DISC1 as a predisposing gene involved in schizophrenia in the Chinese Han Population.However,no positive association is found between DISC1 polymorphisms with schizophrenia clinical symptoms.