Morphological and biochemical repercussions of Toxoplasma gondii infection in a 3D human brain neurospheres model

Autores
Correa Leite, Paulo Emilio; de Araujo Portes, Juliana; Rodrigues Pereira, Mariana; Baldino Russo, Fabiele; Martins Duarte, Erica S.; Almeida dos Santos, Nathalia; Attias, Marcia; Barrantes, Francisco Jose; Baleeiro Beltrão Braga, Patricia Cristina; de Souza, Wanderley
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Toxoplasmosis is caused by the parasite Toxoplasma gondii that can infect the central nervous system (CNS), promoting neuroinflammation, neuronal loss, neurotransmitter imbalance and behavioral alterations. T. gondii infection is also related to neuropsychiatric disorders such as schizophrenia. The pathogenicity and inflammatory response in rodents are different to the case of humans, compromising the correlation between the behavioral alterations and physiological modifications observed in the disease. In the present work we used BrainSpheres, a 3D CNS model derived from human pluripotent stem cells (iPSC), to investigate the morphological and biochemical repercussions of T. gondii infection in human neural cells. Methods: We evaluated T. gondii ME49 strain proliferation and cyst formation in both 2D cultured human neural cells and BrainSpheres. Aspects of cell morphology, ultrastructure, viability, gene expression of neural phenotype markers, as well as secretion of inflammatory mediators were evaluated for 2 and 4 weeks post infection in BrainSpheres. Results: T. gondii can infect BrainSpheres, proliferating and inducing cysts formation, neural cell death, alteration in neural gene expression and triggering the release of several inflammatory mediators. Conclusions: BrainSpheres reproduce many aspects of T. gondii infection in human CNS, constituting a useful model to study the neurotoxicity and neuroinflammation mediated by the parasite. In addition, these data could be important for future studies aiming at better understanding possible correlations between psychiatric disorders and human CNS infection with T. gondii.
Fil: Correa Leite, Paulo Emilio. Universidade Federal do Rio de Janeiro; Brasil
Fil: de Araujo Portes, Juliana. Universidade Federal do Rio de Janeiro; Brasil
Fil: Rodrigues Pereira, Mariana. Universidade Federal Fluminense; Brasil
Fil: Baldino Russo, Fabiele. Universidade Federal de Sao Paulo.; Brasil
Fil: Martins Duarte, Erica S.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Almeida dos Santos, Nathalia. Universidade Federal de Sao Paulo.; Brasil
Fil: Attias, Marcia. Universidade Federal do Rio de Janeiro; Brasil
Fil: Barrantes, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Baleeiro Beltrão Braga, Patricia Cristina. Universidade Federal de Sao Paulo.; Brasil
Fil: de Souza, Wanderley. Universidade Federal do Rio de Janeiro; Brasil
Materia
BRAIN
INFLAMMATION
IPSC
NEUROPSYCHIATRIC DISORDERS
TOXOPLASMOSIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/170173
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/170173
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Morphological and biochemical repercussions of Toxoplasma gondii infection in a 3D human brain neurospheres modelCorrea Leite, Paulo Emiliode Araujo Portes, JulianaRodrigues Pereira, MarianaBaldino Russo, FabieleMartins Duarte, Erica S.Almeida dos Santos, NathaliaAttias, MarciaBarrantes, Francisco JoseBaleeiro Beltrão Braga, Patricia Cristinade Souza, WanderleyBRAININFLAMMATIONIPSCNEUROPSYCHIATRIC DISORDERSTOXOPLASMOSIShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Toxoplasmosis is caused by the parasite Toxoplasma gondii that can infect the central nervous system (CNS), promoting neuroinflammation, neuronal loss, neurotransmitter imbalance and behavioral alterations. T. gondii infection is also related to neuropsychiatric disorders such as schizophrenia. The pathogenicity and inflammatory response in rodents are different to the case of humans, compromising the correlation between the behavioral alterations and physiological modifications observed in the disease. In the present work we used BrainSpheres, a 3D CNS model derived from human pluripotent stem cells (iPSC), to investigate the morphological and biochemical repercussions of T. gondii infection in human neural cells. Methods: We evaluated T. gondii ME49 strain proliferation and cyst formation in both 2D cultured human neural cells and BrainSpheres. Aspects of cell morphology, ultrastructure, viability, gene expression of neural phenotype markers, as well as secretion of inflammatory mediators were evaluated for 2 and 4 weeks post infection in BrainSpheres. Results: T. gondii can infect BrainSpheres, proliferating and inducing cysts formation, neural cell death, alteration in neural gene expression and triggering the release of several inflammatory mediators. Conclusions: BrainSpheres reproduce many aspects of T. gondii infection in human CNS, constituting a useful model to study the neurotoxicity and neuroinflammation mediated by the parasite. In addition, these data could be important for future studies aiming at better understanding possible correlations between psychiatric disorders and human CNS infection with T. gondii.Fil: Correa Leite, Paulo Emilio. Universidade Federal do Rio de Janeiro; BrasilFil: de Araujo Portes, Juliana. Universidade Federal do Rio de Janeiro; BrasilFil: Rodrigues Pereira, Mariana. Universidade Federal Fluminense; BrasilFil: Baldino Russo, Fabiele. Universidade Federal de Sao Paulo.; BrasilFil: Martins Duarte, Erica S.. Universidade Federal do Rio de Janeiro; BrasilFil: Almeida dos Santos, Nathalia. Universidade Federal de Sao Paulo.; BrasilFil: Attias, Marcia. Universidade Federal do Rio de Janeiro; BrasilFil: Barrantes, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Baleeiro Beltrão Braga, Patricia Cristina. Universidade Federal de Sao Paulo.; BrasilFil: de Souza, Wanderley. Universidade Federal do Rio de Janeiro; BrasilElsevier2021-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/170173Correa Leite, Paulo Emilio; de Araujo Portes, Juliana; Rodrigues Pereira, Mariana; Baldino Russo, Fabiele; Martins Duarte, Erica S.; et al.; Morphological and biochemical repercussions of Toxoplasma gondii infection in a 3D human brain neurospheres model; Elsevier; Brain, Behavior, & Immunity - Health; 11; 2-2021; 100190-1002002666-3546CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S2666354620301551info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbih.2020.100190info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:44:12Zoai:ri.conicet.gov.ar:11336/170173instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:44:12.766CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Morphological and biochemical repercussions of Toxoplasma gondii infection in a 3D human brain neurospheres model
title Morphological and biochemical repercussions of Toxoplasma gondii infection in a 3D human brain neurospheres model
spellingShingle Morphological and biochemical repercussions of Toxoplasma gondii infection in a 3D human brain neurospheres model
Correa Leite, Paulo Emilio
BRAIN
INFLAMMATION
IPSC
NEUROPSYCHIATRIC DISORDERS
TOXOPLASMOSIS
title_short Morphological and biochemical repercussions of Toxoplasma gondii infection in a 3D human brain neurospheres model
title_full Morphological and biochemical repercussions of Toxoplasma gondii infection in a 3D human brain neurospheres model
title_fullStr Morphological and biochemical repercussions of Toxoplasma gondii infection in a 3D human brain neurospheres model
title_full_unstemmed Morphological and biochemical repercussions of Toxoplasma gondii infection in a 3D human brain neurospheres model
title_sort Morphological and biochemical repercussions of Toxoplasma gondii infection in a 3D human brain neurospheres model
dc.creator.none.fl_str_mv Correa Leite, Paulo Emilio
de Araujo Portes, Juliana
Rodrigues Pereira, Mariana
Baldino Russo, Fabiele
Martins Duarte, Erica S.
Almeida dos Santos, Nathalia
Attias, Marcia
Barrantes, Francisco Jose
Baleeiro Beltrão Braga, Patricia Cristina
de Souza, Wanderley
author Correa Leite, Paulo Emilio
author_facet Correa Leite, Paulo Emilio
de Araujo Portes, Juliana
Rodrigues Pereira, Mariana
Baldino Russo, Fabiele
Martins Duarte, Erica S.
Almeida dos Santos, Nathalia
Attias, Marcia
Barrantes, Francisco Jose
Baleeiro Beltrão Braga, Patricia Cristina
de Souza, Wanderley
author_role author
author2 de Araujo Portes, Juliana
Rodrigues Pereira, Mariana
Baldino Russo, Fabiele
Martins Duarte, Erica S.
Almeida dos Santos, Nathalia
Attias, Marcia
Barrantes, Francisco Jose
Baleeiro Beltrão Braga, Patricia Cristina
de Souza, Wanderley
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BRAIN
INFLAMMATION
IPSC
NEUROPSYCHIATRIC DISORDERS
TOXOPLASMOSIS
topic BRAIN
INFLAMMATION
IPSC
NEUROPSYCHIATRIC DISORDERS
TOXOPLASMOSIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Toxoplasmosis is caused by the parasite Toxoplasma gondii that can infect the central nervous system (CNS), promoting neuroinflammation, neuronal loss, neurotransmitter imbalance and behavioral alterations. T. gondii infection is also related to neuropsychiatric disorders such as schizophrenia. The pathogenicity and inflammatory response in rodents are different to the case of humans, compromising the correlation between the behavioral alterations and physiological modifications observed in the disease. In the present work we used BrainSpheres, a 3D CNS model derived from human pluripotent stem cells (iPSC), to investigate the morphological and biochemical repercussions of T. gondii infection in human neural cells. Methods: We evaluated T. gondii ME49 strain proliferation and cyst formation in both 2D cultured human neural cells and BrainSpheres. Aspects of cell morphology, ultrastructure, viability, gene expression of neural phenotype markers, as well as secretion of inflammatory mediators were evaluated for 2 and 4 weeks post infection in BrainSpheres. Results: T. gondii can infect BrainSpheres, proliferating and inducing cysts formation, neural cell death, alteration in neural gene expression and triggering the release of several inflammatory mediators. Conclusions: BrainSpheres reproduce many aspects of T. gondii infection in human CNS, constituting a useful model to study the neurotoxicity and neuroinflammation mediated by the parasite. In addition, these data could be important for future studies aiming at better understanding possible correlations between psychiatric disorders and human CNS infection with T. gondii.
Fil: Correa Leite, Paulo Emilio. Universidade Federal do Rio de Janeiro; Brasil
Fil: de Araujo Portes, Juliana. Universidade Federal do Rio de Janeiro; Brasil
Fil: Rodrigues Pereira, Mariana. Universidade Federal Fluminense; Brasil
Fil: Baldino Russo, Fabiele. Universidade Federal de Sao Paulo.; Brasil
Fil: Martins Duarte, Erica S.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Almeida dos Santos, Nathalia. Universidade Federal de Sao Paulo.; Brasil
Fil: Attias, Marcia. Universidade Federal do Rio de Janeiro; Brasil
Fil: Barrantes, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Baleeiro Beltrão Braga, Patricia Cristina. Universidade Federal de Sao Paulo.; Brasil
Fil: de Souza, Wanderley. Universidade Federal do Rio de Janeiro; Brasil
description Background: Toxoplasmosis is caused by the parasite Toxoplasma gondii that can infect the central nervous system (CNS), promoting neuroinflammation, neuronal loss, neurotransmitter imbalance and behavioral alterations. T. gondii infection is also related to neuropsychiatric disorders such as schizophrenia. The pathogenicity and inflammatory response in rodents are different to the case of humans, compromising the correlation between the behavioral alterations and physiological modifications observed in the disease. In the present work we used BrainSpheres, a 3D CNS model derived from human pluripotent stem cells (iPSC), to investigate the morphological and biochemical repercussions of T. gondii infection in human neural cells. Methods: We evaluated T. gondii ME49 strain proliferation and cyst formation in both 2D cultured human neural cells and BrainSpheres. Aspects of cell morphology, ultrastructure, viability, gene expression of neural phenotype markers, as well as secretion of inflammatory mediators were evaluated for 2 and 4 weeks post infection in BrainSpheres. Results: T. gondii can infect BrainSpheres, proliferating and inducing cysts formation, neural cell death, alteration in neural gene expression and triggering the release of several inflammatory mediators. Conclusions: BrainSpheres reproduce many aspects of T. gondii infection in human CNS, constituting a useful model to study the neurotoxicity and neuroinflammation mediated by the parasite. In addition, these data could be important for future studies aiming at better understanding possible correlations between psychiatric disorders and human CNS infection with T. gondii.
publishDate 2021
dc.date.none.fl_str_mv 2021-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/170173
Correa Leite, Paulo Emilio; de Araujo Portes, Juliana; Rodrigues Pereira, Mariana; Baldino Russo, Fabiele; Martins Duarte, Erica S.; et al.; Morphological and biochemical repercussions of Toxoplasma gondii infection in a 3D human brain neurospheres model; Elsevier; Brain, Behavior, & Immunity - Health; 11; 2-2021; 100190-100200
2666-3546
CONICET Digital
CONICET
url http://hdl.handle.net/11336/170173
identifier_str_mv Correa Leite, Paulo Emilio; de Araujo Portes, Juliana; Rodrigues Pereira, Mariana; Baldino Russo, Fabiele; Martins Duarte, Erica S.; et al.; Morphological and biochemical repercussions of Toxoplasma gondii infection in a 3D human brain neurospheres model; Elsevier; Brain, Behavior, & Immunity - Health; 11; 2-2021; 100190-100200
2666-3546
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S2666354620301551
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbih.2020.100190
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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