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

• Autores: Leite, Paulo Emilio Correa; Araujo Portes, Juliana de; Rodrigues Pereira, Mariana; Baldino Russo, Fabiele; Martins-Duarte, Erica S.; Almeida, Nathalia dos Santos; Attias, Marcia; Barrantes, Francisco José; Baleeiro Beltrão-Braga, Patricia Cristina; Souza, Wanderley de
• Año de publicación: 2021
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Brain, Behavior, & Immunity - Health Vol.11, 100190, 2021
• Materia: TOXOPLASMA GONDII; TRASTORNOS NEUROPSIQUIATRICOS; INFLAMACION; CEREBRO
• Institución: Pontificia Universidad Católica Argentina

Fil: Leite, Paulo Emilio Correa. Institute of Biophysics Carlos Chagas Filho; Brasil
Fil: Leite, Paulo Emilio Correa. National Center for Structural Biology and Bioimaging; Brasil
Fil: Leite, Paulo Emilio Correa. Federal University of Rio de Janeiro; Brasil
Fil: Leite, Paulo Emilio Correa. Directory of Metrology Applied to Life Sciences; Brasil
Fil: Leite, Paulo Emilio Correa. National Institute of Metrology Quality and Technology; Brasil
Fil: Araujo Portes, Juliana de. Institute of Biophysics Carlos Chagas Filho; Brasil
Fil: Araujo Portes, Juliana de. National Center for Structural Biology and Bioimaging; Brasil
Fil: Araujo Portes, Juliana de. Federal University of Rio de Janeiro; Brasil
Fil: Rodrigues Pereira, Mariana. Fluminense Federal University. Biology Institute; Brasil
Fil: Baldino Russo, Fabiele. University of Sao Paulo. Institute of Biomedical Science,; Brasil
Fil: Baldino Russo, Fabiele. Laboratory of Disease Modeling, Department of Microbiology; Brasil
Fil: Martins-Duarte, Erica S. Institute of Biophysics Carlos Chagas Filho; Brasil
Fil: Martins-Duarte, Erica S. National Center for Structural Biology and Bioimaging; Brasil
Fil: Martins-Duarte, Erica S. Federal University of Rio de Janeiro; Brasil
Fil: Martins-Duarte, Erica S. Federal University of Minas Gerais. Department of Parasitology; Brasil
Fil: Almeida, Nathalia dos Santos. Laboratory of Disease Modeling, Department of Microbiology; Brasil
Fil: Almeida, Nathalia dos Santos. University of Sao Paulo. Institute of Biomedical Science; Brasil
Fil: Attias, Marcia. Institute of Biophysics Carlos Chagas Filho; Brasil
Fil: Attias, Marcia. National Center for Structural Biology and Bioimaging; Brasil
Fil: Attias, Marcia. Federal University of Rio de Janeiro; Brasil
Fil: Barrantes, Francisco José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Barrantes, Francisco José. Instituto de Investigaciones Biomédicas. Laboratorio de Neurobiología Molecular; Argentina
Fil: Baleeiro Beltrão-Braga, Patricia Cristina. Laboratory of Disease Modeling, Department of Microbiology; Brasil
Fil: Baleeiro Beltrão-Braga, Patricia Cristina. University of Sao Paulo. Institute of Biomedical Science; Brasil
Fil: Baleeiro Beltrão-Braga, Patricia Cristina. Scientific Platform Pasteur-USP
Fil: Souza, Wanderley de. Institute of Biophysics Carlos Chagas Filho; Brasil
Fil: Souza, Wanderley de. National Center for Structural Biology and Bioimaging; Brasil
Fil: Souza, Wanderley de. Federal University of Rio de Janeiro; Brasil
Abstract: 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.