Toxoplasma gondii infection impairs radial glia differentiation and its potential to modulate brain microvascular endothelial cell function in the cerebral cortex

dc.creatorMarcos, Anne Caroline
dc.creatorSiqueira, Michele
dc.creatorAlvarez-Rosa, Liandra
dc.creatorCascabulho, Cynthia M.
dc.creatorWaghabi, Mariana C.
dc.creatorBarbosa, Helene S.
dc.creatorAdesse, Daniel
dc.creatorStipursky, Joice
dc.date2020-07-24T20:29:08Z
dc.date2020-07-24T20:29:08Z
dc.date2020
dc.date.accessioned2023-09-26T20:49:50Z
dc.date.available2023-09-26T20:49:50Z
dc.identifierMARCOS, Anne Caroline et al. Toxoplasma gondii infection impairs radial glia differentiation and its potential to modulate brain microvascular endothelial cell function in the cerebral cortex. Microvascular Research, v. 131, 104204, 12p, June 2020.
dc.identifier0026-2862
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/42389
dc.identifier10.1016/j.mvr.2020.104024
dc.identifier1095-9319
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8864636
dc.descriptionAcesso aberto em 24/07/2020 - https://www.sciencedirect.com/science/article/pii/S0026286220300844
dc.descriptionCongenital toxoplasmosis is a parasitic disease that occurs due vertical transmission of the protozoan Toxoplasma gondii (T. gondii) during pregnancy. The parasite crosses the placental barrier and reaches the developing brain, infecting progenitor, glial, neuronal and vascular cell types. Although the role of Radial glia (RG) neural stem cells in the development of the brain vasculature has been recently investigated, the impact of T. gondii infection in these events is not yet understood. Herein, we studied the role of T. gondii infection on RG cell function and its interaction with endothelial cells. By infecting isolated RG cultures with T. gondii tachyzoites, we observed a cytotoxic effect with reduced numbers of RG populations together with decrease neuronal and oligodendrocyte progenitor populations. Conditioned medium (CM) from RG control cultures increased ZO-1 protein levels and organization on endothelial bEnd.3 cells membranes, which was impaired by CM from infected RG, accompanied by decreased trans-endothelial electrical resistance (TEER). ELISA assays revealed reduced levels of anti-inflammatory cytokine TGF-β1 in CM from T. gondii-infected RG cells. Treatment with recombinant TGF-β1 concomitantly with CM from infected RG cultures led to restoration of ZO-1 staining in bEnd.3 cells. Congenital infection in Swiss Webster mice led to abnormalities in the cortical microvasculature in comparison to uninfected embryos. Our results suggest that infection of RG cells by T. gondii negatively modulates cytokine secretion, which might contribute to endothelial loss of barrier properties, thus leading to impairment of neurovascular interaction establishment.
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsopen access
dc.subjectToxoplasma gondii
dc.subjectToxoplasmose Congênita
dc.subjectDesenvolvimento cerebral
dc.subjectNeurogênese
dc.subjectCélulas endoteliais
dc.subjectBarreira hemencefálica
dc.subjectCongenital toxoplasmosis
dc.subjectToxoplasma gondii
dc.subjectTORCH
dc.subjectRadial glia
dc.subjectEndothelial cells
dc.subjectBrain development
dc.subjectNeurogenesis
dc.subjectBlood-brain barrier
dc.titleToxoplasma gondii infection impairs radial glia differentiation and its potential to modulate brain microvascular endothelial cell function in the cerebral cortex
dc.typeArticle


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