The Molecular Mechanism And Signal Pathway Of Mental And Behaviour Disorder Induced By Toxoplasma Gondii Infection

Toxoplasma gondii(T.gondii),an intracellular parasite,is a zoonotic pathogen that can infect a wide range of animals,including humans.It is generally believed that damage occurs only in fetuses or immune-compromised persons,while in immunocompetent people,the parasite remains as a chronic cryptic,latent brain infection that is clinically asymptomatic.However,recent studies have suggested that a chronic T.gondii infection may alter human behavior and cognitive functions and may even increase the risk of neurological diseases.What is the mechanism that T.gondii lead to the disorder of behavior and mental in mice?Combining the research situation home and abroad,the formation of cysts,the damage of nerve cells and the abnormal secretion of neurotransmitters which caused by T.gondii to be candidates for the underlying causes of the behavioral changes.T.gondii is neurotrophic which can cross the blood-brain barrier to infect the central nervous system.With the immune responses of the host,tachyzoites can transform into bradyzoite to form cysts in CNS,inducing the injury of CNS.In addition,the expression of neurotransmitters in toxoplasmosis which may be an important reason about the abnormal behavior and mental in T.gondii infected mice.However,the exact mechanism remains poorly studied and explained.Deeply research should be down to analyze the behavior and mental changes caused by T.gondii.In this essay,we firstly set up mice with the type II strain of T.gondii(Pru strain).And a series of behavioral tests were performed with mice to characterize and evaluate the behavioral changes.We further detected the pathological injury in brain tissues of infected mice using immunohistochemistry,immunofluorescence staining and western blot.In order to better understand the inflammatory response in CNS in infected mice,RT2 Profiler PCR Array and ELISA were used to profile expression of cytokines and chemokines and NF-κB inflammation signal pathway.In addition,neurotransmitters secretion and the relative neruo signal pathway were studied by HPLC and RT2 Profiler PCR Array.Our results show that T.gondii suppressed the retention of spatial memory but not the ability to learn in the infected mice and contributed to enhanced anxiety levels and decreased exploratory activity in mice.Also,T.gondii infection could cause depression-like behavior in infected mice.Our pathological findings in the context of this chronic infection included rare encysted bradyzoites.Cysts were found in the cortex and striatum,and the cysts in the brain parenchyma were usually remote from areas of inflammation and calcifications and were separated from areas of perivascular and intra-parenchymal inflammation.Also the expression of cytokines and chemokines had varying degrees of change in CNS of sick mice.The activation of NF-κB signal pathway and abnormal of DA signal pathway were detected by RT2 Profiler PCR Array.HPLC showed the expression of neurotransmitters were abnormal in the sick brain.The expression of NE and 5-HT were decreased in infected mice compared with the control mice(P<0.05).While he expression of DA and E were increased in infected mice brain(P<0.05).In summary,in infected mice brain,the activation of astrocyte and microglia causes nerve inflammation which led to neuronal injury in the pathogenesis of toxoplasmosis.The NF-κB signal pathway strengthen the inflammatory response that leads to dysregulated dopaminergic and serotonergic neurotransmitter system.Variation of neurotransmitters in the brain may have implications for understanding the mental and behavior disorder in inhabited host.