Toxoplasma gondii infection damages the perineuronal nets in a murine model

Abstract

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.

Behavioral alterations in long-term Toxoplasma gondii infection of C57BL/6 mice are associated with neuroinflammation and disruption of the blood brain barrier

“…gondii infection in 6 to 18-year-old children, suggesting a role for the parasite infection in the exacerbation of ADHD [ 68 ]. Therefore, our results supporting hyperactivity in the OFT, depicted as increased velocity and total distance covered, corroborate the description of hyperactivity in the type II Prugniaud strain-infected BALB/cJ mice [ 22 , 69 ], C57BL/6J infected with genetically modified ME-49 tachyzoites [ 20 ], and Swiss Webster infected with the ME-49 strain [ 19 ]. Notably, in our model regardless of the reduction in the number of brain cysts, the described behavioral changes were sustained at 60 and 90 dpi.…”

“…The presence of anxiety, revealed as decreased time expended in the central area of the OFT, was detected in the early and long-term chronic infection of C57BL/6 mice with the ME-49 strain. Recently, similar results were shown in the model of early (30 dpi) chronic T. gondii infection of Swiss Webster mice [19]. In experimental models, TST and FST are widely used to assess depressive-like behavior in infectious and non-infectious diseases [24,[56][57][58].…”

“…Recently, similar results were shown in the model of early (30 dpi) chronic T . gondii infection of Swiss Webster mice [ 19 ]. In experimental models, TST and FST are widely used to assess depressive-like behavior in infectious and non-infectious diseases [ 24 , 56 – 58 ].…”

“…gondii [ 16 ] and show behavioral abnormalities. In experimentally infected mice, among the reported behavioral changes are loss of predator fear [ 17 , 18 ], decreased anxiety [ 10 ], increased exploratory behavior [ 19 , 20 ] and impairment of long-term memory during chronic infection [ 21 ]. All these findings contributed to the hypothesis of host manipulation by the parasite, contributing to exposition to definitive host predator and T .…”

Epigenetic Manipulation of Psychiatric Behavioral Disorders Induced by Toxoplasma gondii

“…Although the rodent model infected with T. gondii is one of the most studied models of parasitic behavioral manipulation ( Afonso et al., 2012 ; Webster et al., 2013 ; Tan and Vyas, 2016 ; Meurer et al., 2020 ; Acquarone et al., 2021 ; Evangelista et al., 2021 ), there is still no study that statistically evaluated the tendency to be preyed upon for infected hosts, and the change pattern in daily behavior of chronically infected mice is not specifically elucidated. Besides, the behavioral effects of animal host are also correlated with the clonal lineage of T. gondii strains; for example, infection of inbred mice with acute virulent type I strains causes little specific behavioral disorders but severe acute sickness ( Soh et al., 2013 ).…”