| Background:Toxoplasma gondii is an opportunistic pathogenic protozoan that widely infects humans and warmblooded animals.It can pass through the brain-blood barrier,and enter the brain tissue.T.gondii is neurotropic and cause brain infection,leading to toxoplasmic encephalitis and neuropsychiatric symptoms.T.gondii infection has been found to increase the risk of neuropsychiatric disorders in human population.Seropositivity of toxoplasmic antibodies has been found being associated with schizophrenia,suicide,depression,and other neuropsychiatric disorders,but the underlying mechanisms are currently unknown.In this study,the transcriptome sequencing technology was used to analyze and compare the brain transcriptome of the mice chronically infected with T.gondii and the healthy mice,to screen the significantly differentially expressed genes(DEGs)at the transcription level,and to verify the molecular signaling pathways related to neuropsychiatric disorders,so as to provide a theoretical basis for exploring of the mechanism of neuropsychiatric disorders caused by chronic T.gondii infection in mice.Methods:sv129 mice were infected with T.gondii ME49 strain to establish a mouse model of T.gondii chronic infection,which was verified by Modified Agglutination Test(MAT).The behavioral tests including Morris water maze,open field test,novel object recognition test,three-box social free exploration test and forced swimming test were performed in mice of the infection group and the control group,to explore the changes of behavior in mice caused by chronic infection with T.gondii.Fresh brain tissues of the infection group and the control group were collected,and total RNA was extracted for transcriptome sequencing.The functions of the DEGs in brain tissue of the two groups were compared and analyzed by informatic analysis.Gene Ontology(GO)cluster analysis and Kyoto Encyclopedia of Genes and Genomes(Kyoto Encyclopedia of Genes and Genomes,Kyoto Encyclopedia of Genes and Genomes,Kyoto Encyclopedia of Genes and Genomes,Kyoto Encyclopedia of Genes and Genomes,respectively)were performed.KEGG)signaling pathway enrichment analysis and other bioinformatics analysis were used to verify the transcriptional levels of the target genes in the brain tissues of the two groups of mice by qRT-PCR.Result:The mouse model of the chronic T.gondii infection was successfully established.Compared to the normal controlled grouop,the mice with chronic T.gondii infection showed a decreased spatial learning ability(P<0.05),decreased spatial memory(P<0.001),cognitive memory decline(P<0.01),decreased anxiety and fear behaviors(P<0.01),decreased sociability(P<0.05)and depression-like symptoms(P<0.001).The transcriptome sequencing identified 2295 DGEs.Among them,2016 DEGs were up-regulated and 279 were down-regulated in the brain tissues of the infected mice,compared with those of the normal controlled mice.These DEGs were mainly involved in the immune system,signal transduction,signal molecules and other signaling pathways.Furthermore,the transcription levels of the key genes in kynurenine pathway,which are related to microglia activation,were significantly up-regulated.Conclusion:The behavioral and brain transcriptome analysis of mice with chronic T gondii infection revealed that,the neuropsychiatric symptoms caused by chronic T.gondii infection,were related to the inflammation and glial cells activation caused by chronic T.gondii infection,and the up-regulatied transcription level of the genes in kynurenine pathway in brain played an important role.This study provides a theoretical basis for exploring of the mechanism of neuropsychiatric abnormalities caused by chronic T.gondii infection in mice. |
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