Abstract
Toxoplasma gondii is an obligate intracellular parasite that causes toxoplasmosis, and its congenital transmission is of paramount concern. During embryonic development, infection with the parasite causes irreversible damage to the still-forming fetus’s central nervous system (CNS). In the pathogenesis of neurotoxoplasmosis, purinergic receptors prejudice neuroprotection, neuroinflammation, and activation of microbicide mechanisms against the parasitic vacuole. This study used curcumin as a treatment for neural precursor cells (NPCs) infected with T. gondii. The congenital toxoplasmosis induction consisted of maternal infection with the VEG strain, and NPCs were obtained from the telencephalon of mouse embryos. Curcumin at increasing concentrations was administered in vitro to analyze NPC metabolic activity, cell number, and size, as well as neurogliogenesis, proving to be effective in recovering the size of infected NPCs. Curcumin partially re-established impaired neurogenesis. Purinergic A1, A2A, and P2X7 receptors may be related to neuroprotection, neuroinflammatory control, and activation of mechanisms for inducing the parasite’s death. ERK 1/2 was highly expressed in infected cells, while its expression rates decreased after the addition of the treatment, highlighting the possible anti-inflammatory action of curcumin. These findings suggest that curcumin treats neurological perturbations induced by toxoplasmosis.
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The data supporting this study’s findings are available from the corresponding author, B.F.B., upon reasonable request.
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Funding
This work was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior CAPES/PROEX process n° 88887.372278/2019–00. H.U. acknowledges grant support from the São Paulo Research Foundation ([Fundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP] Proc. No. 2018/07366–4), the National Counsel of Technological and Scientific Development CNPq for grants and fellowships (Proc. No. 406396/2021–3 and 306392/2017–8, respectively), and the National Institute of Science and Technology in Regenerative Medicine (INCT-REGENERA) in Brazil.
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B.F.B., P.M.C., T.V., M.M.P., and N.B.B. performed the experiments. B.F.B. also analyzed the data and wrote the manuscript. V.M.M.M., N.B.B., C.M.A., and A.S.S. revised the manuscript and provided reagents. H.U. contributed to manuscript writing and critically revised the manuscript. All authors read and approved the publication of this manuscript.
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Bissacotti, B.F., Copetti, P.M., Bottari, N.B. et al. Curcumin modulates neurogliogenesis and purinergic receptor expression in neural precursor cells infected with Toxoplasma gondii. Parasitol Res 122, 77–84 (2023). https://doi.org/10.1007/s00436-022-07698-y
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DOI: https://doi.org/10.1007/s00436-022-07698-y