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Resveratrol as a Therapy to Restore Neurogliogenesis of Neural Progenitor Cells Infected by Toxoplasma gondii

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Abstract

The intracellular protozoan Toxoplasma gondii may cause congenital toxoplasmosis and serious brain damage in fetus. However, the underlying mechanism of neuropathogenesis in brain toxoplasmosis remains unclear. For this study, neural progenitor cells (NPCs) were obtained from embryo telencephalons (embryonic day 13) and induced to proliferation in the presence of growth factors (GFs). For gathering insights into the biological effects of resveratrol (RSV) on neurogenesis, this study aimed to investigate effects of RSV concentrations (0.1 to 100 μM) on proliferation, migration and differentiation of NPCs infected by T. gondii. T. gondii infection increased the presence of cells in Sub G1 phase, reducing the global frequency of undifferentiated cells in S and G2/M phases of cell cycle and reduced cell viability/mithochondrial activity of infected NPCs. Moreover T. gondii stimulated neural migration and gliogenesis during neutral differentation. However, the treatment with RSV stimulated cell proliferation, restored cellular viability of infected NPCs and exerted an inhibitory effect on gliogenesis of infected NPCs favorecing neuronal maturation during toxoplasmosis infection. Thus, we have successfully to demonstrated that RSV is promising as therapeutic for congenital toxoplasmosis.

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Funding

This work was supported by the Coordenação de Aperfeiçoamento Pessoal de Nível Superior (CAPES), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq - Project N°. 304,328/2015–4), Brazil. MPP acknowledges postdoctoral fellowship support by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP Project N°. 2015/19478–3). H.U. acknowledges grant support from FAPESP for investigating mechanisms of neurogenesis (Project N°. 2012/50880–4).

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Authors and Affiliations

  1. Graduate Program in Toxicological Biochemical and Department of Biochemistry and Molecular Biology, Universidade Federal de Santa Maria (UFSM), Avenida Roraima, n°1000, Camobi District, Zip Code, Santa Maria, 97105900, Brazil

    Nathieli B. Bottari, Maria Rosa C. Schetinger, Thais V. Palma, Mariana S. Alves, Vera M. Morsch, Cinthia Melazzo & Aleksandro Schafer Da Silva

  2. Department of Biochemistry, Institute of Chemistry, Universidade de São Paulo (USP), São Paulo, SP, Brazil

    Micheli M. Pillat & Henning Ulrich

  3. Department of Preventive Veterinary Medicine, Universidade Estadual de Londrina (UEL), Londrina, Paraná, PR, Brazil

    Luiz Daniel de Barros & João Luis Garcia

  4. Graduate Program in Animal Science, Universidade do Estado de Santa Catarina (UDESC), Chapecó, SC, Brazil

    Aleksandro Schafer Da Silva

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  1. Nathieli B. Bottari
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  2. Maria Rosa C. Schetinger
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  3. Micheli M. Pillat
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Correspondence to Aleksandro Schafer Da Silva.

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Bottari, N.B., Schetinger, M.R.C., Pillat, M.M. et al. Resveratrol as a Therapy to Restore Neurogliogenesis of Neural Progenitor Cells Infected by Toxoplasma gondii. Mol Neurobiol 56, 2328–2338 (2019). https://doi.org/10.1007/s12035-018-1180-z

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