| Objectives: To explore the relationship between herpes simplex virus(HSV)infection and cognitive dysfunction.Methods: 1.The study construct a BALB/c mouse model of HSV-2 vaginal infection,analyze the protein expression differences in BALB/c mouse brain tissues after HSV-2 infection by label-free quantitative proteomics,and perform GO annotation and KEGG analysis on the differential proteins,and verify the expression of some differential proteins by western blotting.2.The study construct HSV-1 corneal infection models of 3 months of age,9 months of age,12 months of age C57BL/6mice,analyze the spatial learning and memory levels of C57BL/6 mice in acute infection and latent infection by Morris water maze detection,detect and analyze the activation of senile plaques and microglia in brain tissues of C57BL/6 mice by morphological staining method,and detect and analyze the expression of Alzheimer’s disease marker molecules Aβ and phosphorylated Tau protein in brain tissues by western blotting.At the same time,APP/PS1 transgenic mice were used as a positive control.Results:1.Based on proteomic analysis,we revealed 249 differentially expressed proteins detected in the brain tissue after HSV-2 infection compared with BALB/c mice in the blank control group,GO annotation analysis of these proteins revealed that they are mainly involved in synapse formation and the regulation of synaptic excitability,KEGG enrichment analysis suggests that they influence autophagy,the development of other neurodegenerative diseases,and signaling pathway genes associated with other neurological diseases.At the same time,brain tissue findings were compared between asymptomatic and symptomatic mice after infection,differential proteins are mainly proteins associated with synaptogenesis and synaptic transmission and are involved in signaling pathways in autophagy,addiction,and other neurological diseases.These results suggest that alterations in synaptic structure and function as well as autophagy may be associated with the development of neurological abnormalities following HSV-2 infection.2.The results of Morris water maze during HSV-1 acute infection showed that C57BL/6 mice at 3 months,9 months,and 12 months of age did not show significant decreases in spatial learning and memory levels,However,only 12-month-old C57BL/6 mice showed a significant decrease in spatial learning and memory levels during the HSV-1 latent infection period.Congo red staining revealed that no significant senile plaques were observed after HSV-1 infection in C57BL/6 mice at 3 months,9 months,and 12 months of age,Immunofluorescence revealed that microglial activation was significantly increased in the brain tissue of 3 mouths mice compared with both the ctrl and APP/PS1 groups after HSV-1 infection,meanwhile,the expression level of Aβ expression was slightly increased in the acute and latent infectious phases compared with the ctrl group.Western blot experiments revealed that C57BL/6 mice at 3 months,9 months,and 12 months of age showed an increase in P-tau expression after HSV-1 infection,In particular,the incubation period after infection,while the expression of Aβ showed a significant increase only after HSV-1 infection in 3-month-old C57BL/6 mice.Conclusion : 1.Infection with herpes zoster virus causes changes in expression of signaling pathway proteins in Alzheimer ’s disease.2.Herpes simplex virus infection can cause a decrease in spatial learning and memory function.3.Spatial learning and memory dysfunction caused by herpes simplex virus infection is associated with abnormal phosphorylation of tau protein. |
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