EEG Study And Bioinformatics Analysis Of SCA3 Mice

Part I :Study of EEG in spinocerebellar ataxia type 3 miceObjective: The purpose of this study is to acquire the EEG signals in the central nervous system of SCA3 mice by using a computer or other electronic communication equipment and control system,then we analyze and identify the certain signals of behaviors in specific regions of the mice brain in the experiment,recording the parameters to make a dis nc on between the groups,and providing new basis to explore the clinical diagnosis and the nature of the disease.Methods: Male SCA3 mice and male wild-type(WT)mice were from Zhengzhou University Animal Center,weight 20-23 g,aged 12 months old SCA3 mice and WT mice in each group,age 1 months during the growth period of a group of mice with SCA3 gene.The self-made electrode was implanted into the brain surface of mice,and the Blackrock cerebus128 channel acquisition system was used to collect and analyze the following data.1.12 month old male SCA3 mice and male WT mice were compared with alpha,beta,theta,and delta four kinds of EEG and LZ complexity.2.12 month old male SCA3 mice and male WT mice were compared with the mean entropy of the field potential and the C0 complexity.3.12 month old male SCA3 mice were compared with 1 month old male SCA3 mice for LZ band complexity.Results: 1.Compared with WT mice,the four bands of energy were significantly higher in 12 month old SCA3 mice model.After t inspection,the P values of the four bands of energy were 0,0.0005,0.0001,0.0013;there were significant differences in LZ complexity,and the beta band is most obvious.2.In the analysis of the presence potentials of 12 month old SCA3 model mice and WT mice,the model group had lower approximate entropy and higher C0 complexity 3.12 month old male SCA3 mice compared with 1 month old male SCA3 mice in the LZ complexity of the beta band,1 month old SCA3 mice had lower LZ complexity,and 12 month old SCA3 mice had higher LZ complexity.Conclusion: Data show that the brain waves in each band of SCA3 mice were strengthened,and can be dis nguished by the LZ complexity of the beta band,Compared with the normal group,the model group had lower value of approximate entropy,and its C0 complexity was higher than normal in the field potential analysis.There were no obvious symptoms in young SCA3 mice,and the characteristics of EEG were similar to that of normal mice.Part II :Bioinformatic analysis of differentially expressed genes in SCA3 miceObjective: To analyze the differen ally expressed genes()DEGs in the cerebellum of spinocerebellar ataxia type 3 transgenic mice and normal wild mice,and explore the pathogenesis of this disease from molecular scale,and elucidate its biological significance of the DEGs.Methods: We obtain the gene expression data sets of cerebellum of transgenic mice by gene chip technology.The data sets contains 10 samples,5 are SCA3 transgenic mice,and 5 are wild type mice.Then NOISeq method was used to deal with microarray data and to screen the differentially expressed genes.All the DEGs were sent to cluster analysis,GO enrichment analysis and Pathway enrichment analysis.Then all the genes were uploaded to STRING interaction database and the protein-protein interaction(PPI)network were constructed.Results: A total of 36 DEGs were found in transgenic mice,of which 4 genes were up-regulated and 32 genes were down regulated.Analysis of biological processes in GO enrichment showed that these genes mainly involved in cell growth,cell cycle,elongation of single and multicellular organisms,multiple biological processes and the control of positive and negative feedback,symbiosis in host growth regula on;response to bacteria,inorganic compounds,metal ions,biological decomposition,external biological stimuli;Molecular func on showed that these genes mainly involved the banding of glycosaminoglycan,metal ions,growth factor,receptor and cationic,catalytic activity and transport activity.The KEGG analysis showed that these genes were mainly involved in the secretion of saliva,transcriptional dysregulation in cancer,tuberculosis,adhesion,amebiasis,gastric acid secretion,porphyrin and chlorophyll metabolism,glycine,serine and threonine metabolism and signal pathways of African trypanosomiasis.PPI network analysis showed that proteins such as Ltf,Ngp,S100a8,S100a9,Mpo and Camp interact with other ≥5 proteins,thus they are the central proteins of the protein-protein interaction network.Conclusion: The up-regulation of Hspb1,Rps27 rt,Eno1b and Nrgn,and the down-regulation of S100a9,S100a8,Ltf,Mpo,Camp,Ngp,Elane,Chi3I3 and Eif2s3 y may be involved in the mechanism of injury of SCA3.Part III : Bioinformatic analysis of differentially expressed micro RNAs in spinocerebellar ataxia type 3 miceObjective: To analyze the difference of micro RNA expression in the hippocampal region of the spinocerebellar ataxia type 3 transgenic mice and the normal wild-type mice,and to explore the pathogenesis of this disease and explore its biological significance.Methods: RNA was extracted from cerebellum,and micro RNA was isolated.Then the mi RNA expression profiles were obtained by microarray,and all screened micro RNA were analyzed by cluster analysis,GO enrichment analysis and Pathway enrichment analysis.Results: A total of 117 differentially expressed micro RNA were found in transgenic mice,55 of which were significantly up-regulated,and 62 of which were significantly downregulated.The biological analysis shows that these differentially expressed micro RNA mainly involving organs,cells,cell protein modification process,cell signal transduction,protein biosynthesis,Ras cell biological adhesion,microtubules,cytoskeleton and cell proliferation.The molecular function showed that these target genes were mainly involved in cation and metal ion binding,GTP enzyme activity regulation,nucleoside three phosphatase activity regulation,adenine nucleotide binding and adenylate cyclase activity.The KEGG analysis showed that the differential expression of micro RNA target genes mainly involved in insulin resistance and transduction,other types of O-glycan biosynthesis pathway,ECM receptor interaction pathway,glycerophospholipid metabolism pathway,glycerophospholipid metabolism,phosphatidylinositol signal system,mannose type O-glycan biosynthesis,metabolism,nicotinic acid and propionic acid nicotinamide metabolism and complement and coagulation cascade pathway.Conclusion: There are 117 differentially expressed micro RNA,of which 55 mi RNA were significantly up-regulated and the others were down-regulated,such as mi R-34 b,mi R-25,and so on,may be involved in the pathogenesis of spinocerebellar ataxia by regulating m RNA.Also,6 key genes were verified by q RT-PCR.