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Zika virus infection impairs synaptogenesis, induces neuroinflammation, and could be an environmental risk factor for autism spectrum disorder outcome.
Ohki, Cristine Marie Yde; Benazzato, Cecília; van der Linden, Vanessa; França, Julia V; Toledo, Carmen M; Machado, Rafael Rahal Guaragna; Araujo, Danielle Bastos; Oliveira, Danielle Bruna Leal; Neris, Romulo S; Assunção-Miranda, Iranaia; de Oliveira Souza, Isis Nem; Nogueira, Clara O; Leite, Paulo Emilio Corrêa; van der Linden, Hélio; Figueiredo, Claudia P; Durigon, Edison Luiz; Clarke, Julia R; Russo, Fabiele Baldino; Beltrão-Braga, Patricia Cristina Baleeiro.
Afiliación
  • Ohki CMY; Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
  • Benazzato C; Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
  • van der Linden V; Barão de Lucena Hospital, Recife, Brazil.
  • França JV; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • Toledo CM; Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
  • Machado RRG; Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
  • Araujo DB; Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
  • Oliveira DBL; Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
  • Neris RS; Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • Assunção-Miranda I; Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • de Oliveira Souza IN; School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • Nogueira CO; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • Leite PEC; Clinical Research Unit of the Antonio Pedro Hospital, Federal Fluminense University, Rio de Janeiro, Brazil.
  • van der Linden H; Rehabilitation Center Dr. Henrique Santillo, Goiania, Brazil.
  • Figueiredo CP; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • Durigon EL; Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Institut Pasteur de São Paulo, São Paulo, Brazil.
  • Clarke JR; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
  • Russo FB; Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
  • Beltrão-Braga PCB; Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Institut Pasteur de São Paulo, São Paulo, Brazil. Electronic address: patriciacbbbraga@usp.br.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167097, 2024 06.
Article en En | MEDLINE | ID: mdl-38408544
ABSTRACT
Zika virus (ZIKV) infection was first associated with Central Nervous System (CNS) infections in Brazil in 2015, correlated with an increased number of newborns with microcephaly, which ended up characterizing the Congenital Zika Syndrome (CZS). Here, we investigated the impact of ZIKV infection on the functionality of iPSC-derived astrocytes. Besides, we extrapolated our findings to a Brazilian cohort of 136 CZS children and validated our results using a mouse model. Interestingly, ZIKV infection in neuroprogenitor cells compromises cell migration and causes apoptosis but does not interfere in astrocyte generation. Moreover, infected astrocytes lost their ability to uptake glutamate while expressing more glutamate transporters and secreted higher levels of IL-6. Besides, infected astrocytes secreted factors that impaired neuronal synaptogenesis. Since these biological endophenotypes were already related to Autism Spectrum Disorder (ASD), we extrapolated these results to a cohort of children, now 6-7 years old, and found seven children with ASD diagnosis (5.14 %). Additionally, mice infected by ZIKV revealed autistic-like behaviors, with a significant increase of IL-6 mRNA levels in the brain. Considering these evidence, we inferred that ZIKV infection during pregnancy might lead to synaptogenesis impairment and neuroinflammation, which could increase the risk for ASD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Astrocitos / Trastorno del Espectro Autista / Virus Zika / Infección por el Virus Zika / Enfermedades Neuroinflamatorias País/Región como asunto: America do sul / Brasil Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Astrocitos / Trastorno del Espectro Autista / Virus Zika / Infección por el Virus Zika / Enfermedades Neuroinflamatorias País/Región como asunto: America do sul / Brasil Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Países Bajos