Toxoplasma gondii infection damages the perineuronal nets in a murine model

BACKGROUND Behavioral and neurochemical alterations associated with toxoplasmosis may be influenced by the persistence of tissue cysts and activation of an immune response in the brain of Toxoplasma gondii-infected hosts. The cerebral extracellular matrix is organised as perineuronal nets (PNNs) that are both released and ensheath by some neurons and glial cells. There is evidences to suggest that PNNs impairment is a pathophysiological mechanism associated with neuropsychiatric conditions. However, there is a lack of information regarding the impact of parasitic infections on the PNNs integrity and how this could affect the host's behavior. OBJECTIVES In this context, we aimed to analyse the impact of T. gondii infection on cyst burden, PNNs integrity, and possible effects in the locomotor activity of chronically infected mice. METHODS We infected mice with T. gondii ME-49 strain. After thirty days, we assessed locomotor performance of animals using the open field test, followed by evaluation of cysts burden and PNNs integrity in four brain regions (primary and secondary motor cortices, prefrontal and somesthetic cortex) to assess the PNNs integrity using Wisteria floribunda agglutinin (WFA) labeling by immunohistochemical analyses. FINDINGS AND MAIN CONCLUSIONS Our findings revealed a random distribution of cysts in the brain, the disruption of PNNs surrounding neurons in four areas of the cerebral cortex and hyperlocomotor behavior in T. gondii-infected mice. These results can contribute to elucidate the link toxoplasmosis with the establishment of neuroinflammatory response in neuropsychiatric disorders and to raise a discussion about the mechanisms related to changes in brain connectivity, with possible behavioral repercussions during chronic T. gondii infection.

The influence of salt intake on the course of experimental toxoplasmosis in outbred or inbred mouse strains

Many environmental factors contribute to an effective immune response against Toxoplasma gondii (Tg) infection, among which diet is important in triggering the immune response of the host to infection. Emerging reports suggest that salt intake undermines the regulatory mechanisms mediated by innate and adaptive immune cells. Unfortunately, the impact of an Intermediate Salt Diet (ISD) on the pathogenesis and immune response to toxoplasmosis remains unclear. The purpose of this study was to evaluate the susceptibility profile to an ISD (NaCl 2%) of two mouse strains (outbred Swiss and inbred C57BL6) infected by the ME49 strain of Tg. Our data confirm an antagonistic susceptibility to oral Tg infection among the two mouse strains. Sodium intake induced the highest mortality in C57BL6 compared to Swiss mice in the infected groups. A simultaneous ISD with the infection did not induce significant differences in body weight in either mouse strains. Both mouse strains showed an antagonistic response to a sodium intake diet on the number of parasite brain cysts. An increased number of brain cysts in C57BL6 ISD-Tg animals were noted while Swiss ISD-Tg animals presented a decrease in the number of brain cysts compared to NSD-Tg (Normal Salt Diet) for both mouse strains. Furthermore, sodium intake caused a significant reduction in the specific humoral immune response against Tg in inbred C57BL6 mice. Thus, our data reveal that an ISD affects the humoral immune response in the murine model and influences the course of Tg infection.