Zika virus infection impairs synaptogenesis, induces neuroinflammation, and could be an environmental risk factor for autism spectrum disorder outcome.

Autor: 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.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2024 Jun; Vol. 1870 (5), pp. 167097. Date of Electronic Publication: 2024 Feb 24.
DOI: 10.1016/j.bbadis.2024.167097
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
Externí odkaz: