Study On The Effect Of The Lack Of Rhythm Gene Per2 On Depression In Mice And Its Mechanism

Objective:Using behavioral methods to study the effect of mouse Per2 gene deletion on the degree of anxiety and depression and the lack of social interaction.Differentially expressed genes(DEGs)were screened using Per2 gene-deficient mice and wild-type mouse gene chips,and these genes were subjected to biological function enrichment analysis,cell pathway enrichment analysis,and protein interaction network analysis to finally screen out Key genes to reveal the mechanism of Per2 depression in mice.Methods:1.Fourteen C57 BL / 6 male mice and 14 Per2 knockout mice were selected.Wild-type mice were randomly divided into a control group and a depression model group.Per2 knockout mice were also randomly divided into a control group and a depression model group.Chronic social frustration stress method was used to construct mouse depression model.The mice in each group were tested in black and white boxes,forced swimming and social interaction.2.Taking GSE4253 chip data in the GEO database of the National Center for Biotechnology Information(NCBI)website as the research object,screening differentially expressed genes in R language,using Cytoscape software to perform enrichment analysis of GO gene function annotations on DEGs,and KOBAS3.0 for online KEGG In the pathway enrichment analysis,STRING online software constructs a protein interaction network,and finally combines key ?log2FC?value,P value,and comprehensive evaluation of GO enrichment and KEGG pathway enrichment results to select key genes.Results:1.In the black-and-white box experiment,the model group of wild-type mice was shorter than the control group(P <0.05),and the Per2 gene knockout depression model mice were also shorter than the control group(P <0.05).The wild control mice were longer than the Per2 knockout control group(P <0.05).The wild-type mouse model group of the immobility time of the forced swimming experiment was shorter than that of the control group(P <0.001),and the De2 knock-out model mice were also shorter than the control group(P <0.05).The wild control mice were longer than the Per2 knockout control group(P <0.05),and the wild model mice were longer than the Per2 knockout model group(P <0.05).The contact time ratio / non-contact time of the social interaction experiment is shorter than that of the wild-type mouse model group compared with the control group(P <0.001),and the Per2 gene knockout depression model mice are also smaller than the control group(P <0.05),wild The mice in the control group were larger than those in the Per2 knockout control group(P <0.05).2.Screened 2609 differential genes,including 1754 up-regulated genes and 855 down-regulated genes.The differential genes of GO function enrichment analysis are mainly distributed in the plasma membrane,development process,regulation of cellular metabolic processes,multicellular biological development,regulation of primary metabolic processes,regulation of macromolecular metabolic processes,development of anatomical structures,regulation of biosynthesis processes,The regulation of cell biosynthesis process,the regulation of nitrogen compound metabolism process,the regulation of gene expression,and the regulation of nucleic acid metabolism process are several functional families.The down-regulated DEGs are mainly involved in plasma membrane,extracellular region,extracellular space,vesicles,microsomes,serine endopeptidase activity,peptidase inhibitor activity,monooxygenase activity.KEGG pathway enrichment analysis The differential genes are mainly enriched in neuroactive ligand-receptor interaction,chemical carcinogenesis,inflammatory mediator regulation of TRP channels,retinol metabolism,linoleic acid metabolism,steroid hormone synthesis,peanut four Enolic acid metabolism,renin-angiotensin system,serotonin synapse,thyroid hormone synthesis,glutamatergic synapse,gastric acid secretion,pancreatic secretions,cytokine and cytokine receptor interactions,endocrine and other Factor-regulated calcium reabsorption.Analysis of the protein interaction network revealed 764 relationships including 605 nodal proteins.Finally,the key genes Gabra2,Gabr2,Gabrq,Lhx1,Dnase1,Drd1 a,Ppp1r1b,Gria1,Slco1c1 were selected.Among these key genes,Dnase1 and Ppp1r1 b are up-regulated genes,and the rest are down-regulated genes.Conclusion:The deletion of Per2 gene can cause depression-like changes in mice,and it can also increase the degree of depression in depressed mice.The main principles of the absence of Per2 leading to the occurrence of depressive disorder are: 1.GABA receptor expression decreases,and GABA plays an important role in emotion regulation.2.The expression of genes that promote the development of nerve cells decreases,while the expression of genes that promote apoptosis increases,which can lead to neurodegenerative lesions.3.Decreased synthesis of dopamine receptors and increased expression of dopamine protein phosphatase inhibitors that inhibit the activation of dopamine signaling pathways reduce the dopamine-mediated fun and motivational experience,which may lead to depressive performance that lacks pleasure.4.Decreased expression of glutamate transporter and glutamate receptors may inhibit the function of excitatory neurotransmitter glutamate,and the level of glutamate in the brain of patients with severe depression may be reduced.5.Thyroid hormone plays an important role in the nervous system.The down-regulation of thyroid hormone transporter in the center will make the center less sensitive to thyroid hormone,which may lead to depression.For the diagnosis and treatment of depression,more attention should be paid to the above aspects.?...