Study On The Relationship Between Schizophrenia Susceptibility Gene NKAPL And Inflammation Activation

BackgroundSchizophrenia(SZ)is a common mental illness,mainly manifested as disorder of emotion,thinking and behavior.A large number of studies have found multiple schizophrenia susceptibility genes through genome-wide association analysis.A considerable number of genes are related to neurodevelopment and inflammation,but lack of in-depth research cannot provide a theoretical basis for the pathological and physiological studies of schizophrenia.Especially in the whole genome analysis of Chinese Han SZ patients,it is found that the unique susceptibility gene NKAPL lacks research.Therefore,exploring the basic biological functions of schizophrenia susceptibility genes provides an important basis for exploring the molecular mechanism of schizophrenia.Objective1.Understand the spatiotemporal expression pattern of NKAPL gene to provide a basis for further research.2.To investigate the correlation between the schizophrenia susceptibility gene NKAPL and nerve development and inflammation through the cell model and BABL/c mouse inflammation model to understand the expression changes of inflammation-related genes NKAPL,NF-?B and inflammatory factors.3.Through the Poly I: C schizophrenic model of progeny during pregnancy,study the changes of NKAPL,provide relevant basis for the pathogenesis of schizophrenia.Methods1.BABL/c mice are used as models,and materials are collected at different time and space points.The total RNA extracted from the material was reverse transcribed into cDNA,and the expression level of NKAPL gene was compared using qPCR technology.At the same time,the material will be extracted to extract the total protein,and the expression level of NKAPL protein will be compared by immunoblotting.2.Inflammation model: LPS stimulates BV2 cells to collect medium supernatant and cells after 12 h.In addition,LPS is injected intraperitoneally to stimulate BALB/c mice for 7 consecutive days,and the corresponding tissues and organs and plasma are taken,using ELISA kit Detection of cytokines,and Western blot detection of normal group and LPS group related protein and NKAPL expression.3.Select BABL/c mice 9 days pregnant and inject 10 mg / kg Poly I: C(n = 10)and an equal volume of 0.9% sterile saline(n = 10)into the tail vein of BABL/c mice.The progeny of the model group and the progeny of the control group were weaned and divided into cages at 21 days of age.Only male rats were selected as the research object,and samples were taken in Postnatal 65 Days(PND65),and related gene expression tests were performed by molecular techniques.Results1.The experiment found that the expression of NKAPL in BABL/c mice is systemic,and its gene expression levels in hippocampus,frontal lobe,cerebellum,cerebral cortex,heart,liver,spleen,lung,kidney,and skeletal muscle are almost in PND2-PND21.The time increases and increases,and tends to be stable at PND21-PND65,and the expression level of mRNA level and protein level are consistent.2.The detection found that LPS stimulated BV2 cells and BABL/c mice whose inflammation level was higher than that of the normal group,and we analyzed the expression levels of NKAPL and inflammatory factors by qPCR,which were higher than that of the normal group.At the same time,immunofluorescence showed that the number of astrocytes and microglia in the LPS group in the hippocampus was significantly higher than that in the PBS group;the number of astrocytes and NKAPL positive cells in the cerebellar LPS group was significantly higher than that in the PBS group.3.The test found that in the schizophrenia Poly I: C pregnancy progeny model,the expression of NKAPL in the adult model group decreased compared with the control group,while the expression level of PSD95 decreased.Conclusions1.The expression of NKAPL gene in BABL/c mice at different time and space,the expression level gradually increased with the development of mice in the early period and stabilized during the weaning period,which revealed that it may be related to development.2.In cell and animal inflammation models,the expression level of NKAPL gene increases,suggesting that NKAPL is related to inflammation pathways.3.The expression level of NKAPL in the progeny model of schizophrenia Poly I:C infection during pregnancy is low,revealing that NKAPL may be related to abnormal neurodevelopment in the schizophrenia model.