Neuroprotective role of resveratrol mediated by purinergic signalling in cerebral cortex of mice infected by Toxoplasma gondii.

The central nervous system of the intermediate host plays a central role in lifelong persistence of Toxoplasma gondii as well as the pathogenesis of congenital toxoplasmosis and reactivated infection in immunocompromised individuals. The purinergic system has been implicated in a wide range of immunological pathways for controlling intracellular responses to pathogens, including T. gondii. In the present study, we investigated the effect of resveratrol (RSV) on ectonucleotidases, adenosine deaminase (ADA), and purinergic receptors during chronic infection by T. gondii. For this study, Swiss mice were divided into control (CTL), resveratrol (RSV), infected (INF), and INF+RSV groups. The animals were orally infected with the VEG strain and treated with RSV (100 mg/kg, orally). Ectonucleotidase activities, P2X7, P2Y1, A1, and A2A purinergic receptor density, ROS, and thiobarbituric acid reactive substances levels were measured in the cerebral cortex of mice. T. gondii infection increased NTPDase and reduced ADA activities. Treatment with RSV also affected enzymes hydrolysing extracellular nucleotides and nucleosides. Finally, RSV affected P1 and P2 purinergic receptor expression during T. gondii infection. Overall, RSV-mediated beneficial changes in purinergic signalling and oxidative stress, possibly improving cerebral cortex homeostasis in T. gondii infection.

Resveratrol-mediated reversal of changes in purinergic signaling and immune response induced by Toxoplasma gondii infection of neural progenitor cells.

The effects of Toxoplasma gondii during embryonic development have not been explored despite the predilection of this parasite for neurons and glial cells. Here, we investigated the activation of the purinergic system and proinflammatory responses during congenital infection by T. gondii. Moreover, neuroprotective and neuromodulatory properties of resveratrol (RSV), a polyphenolic natural compound, were studied in infected neuronal progenitor cells (NPCs). For this study, NPCs were isolated from the telencephalon of infected mouse embryos and subjected to neurosphere culture in the presence of EGF and FGF2. ATP hydrolysis and adenosine deamination by adenosine deaminase activity were altered in conditions of T. gondii infection. P2X7 and adenosine A2A receptor expression rates were augmented in infected NPCs together with an increase of proinflammatory (INF-γ and TNF-α) and anti-inflammatory (IL-10) cytokine gene expression. Our results confirm that RSV counteracted T. gondii-promoted effects on enzymes hydrolyzing extracellular nucleotides and nucleosides and also upregulated P2X7 and A2A receptor expression and activity, modulating INF-γ, TNF-α, and IL-10 cytokine production, which plays an integral role in the immune response against T. gondii.