Toxoplasma gondii infection impairs radial glia differentiation and its potential to modulate brain microvascular endothelial cell function in the cerebral cortex.
Microvasc Res
; 131: 104024, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32502488
ABSTRACT
Congenital 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-ß1 in CM from T. gondii-infected RG cells. Treatment with recombinant TGF-ß1 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Toxoplasma
/
Diferenciação Celular
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Córtex Cerebral
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Toxoplasmose Congênita
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Toxoplasmose Cerebral
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Células Endoteliais
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Microvasos
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Células Ependimogliais
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Acoplamento Neurovascular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Microvasc Res
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Brasil