Chronic Toxoplasma gondii infection contributes to perineuronal nets impairment in the primary somatosensory cortex.

Toxoplasma gondii is able to manipulate the host immune system to establish a persistent and efficient infection, contributing to the development of brain abnormalities with behavioral repercussions. In this context, this work aimed to evaluate the effects of T. gondii infection on the systemic inflammatory response and structure of the primary somatosensory cortex (PSC). C57BL/6 and BALB/c mice were infected with T. gondii ME49 strain tissue cysts and accompanied for 30 days. After this period, levels of cytokines IFN-γ, IL-12, TNF-α and TGF-ß were measured. After blood collection, mice were perfused and the brains were submitted to immunohistochemistry for perineuronal net (PNN) evaluation and cyst quantification. The results showed that C57BL/6 mice presented higher levels of TNF-α and IL-12, while the levels of TGF-ß were similar between the two mouse lineages, associated with the elevated number of tissue cysts, with a higher occurrence of cysts in the posterior area of the PSC when compared to BALB/c mice, which presented a more homogeneous cyst distribution. Immunohistochemistry analysis revealed a greater loss of PNN labeling in C57BL/6 animals compared to BALB/c. These data raised a discussion about the ability of T. gondii to stimulate a systemic inflammatory response capable of indirectly interfering in the brain structure and function.

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.

Evidence of an inverse correlation between serotonergic activity and spreading depression propagation in the rat cortex.

Various neurological and psychiatric diseases lead to alterations in cortical serotonergic activity as one of their underlying processes. However, the electrophysiological implication of changes in serotonergic activity remains a matter of investigation. In this study, we investigated whether brain serotonergic activity influences the excitability-related phenomenon known as cortical spreading depression (CSD). CSD parameters (propagation velocity, and amplitude and duration of the DC-shift) was evaluated in rats that received two treatments that increased cortical serotonergic activity, electrical stimulation of the raphe nuclei and subcutaneous injection of a selective serotonin reuptake inhibitor, sumatriptan. A third group of rats was tested on a low-tryptophan diet rat model of serotonin depletion. Control rats for these three groups received, respectively, sham raphe stimulation, saline injection, and a tryptophan-supplemented diet. Compared to controls, electrical stimulation of the raphe nuclei and sumatriptan administration decelerated CSD and increased the duration of the negative DC-shift of CSD, whereas the low-tryptophan diet was associated with significantly accelerated CSD propagation and shortened DC-shift of CSD (p<0.05). We concluded that serotonergic neurons are very important for stabilizing the delicate equilibrium between excitatory and inhibitory neuronal influences that determines cortical excitability and CSD propagation. Our pharmacological, electrophysiological and dietary data suggest that cortical serotonergic activity negatively modulates CSD propagation in the rat cortex. Reduced central serotonergic activity, as can be observed in several neurological and psychiatric diseases, may constitute a pathological factor for increased sensitivity to CSD.