Zika virus vertical transmission induces neuroinflammation and synapse impairment in brain cells derived from children born with Congenital Zika Syndrome.
Humans
Zika Virus Infection
/ virology
Female
Zika Virus
/ pathogenicity
Synapses
/ pathology
Brain
/ virology
Infectious Disease Transmission, Vertical
Pregnancy
Induced Pluripotent Stem Cells
/ metabolism
Neurons
/ virology
Male
Astrocytes
/ virology
Neuroinflammatory Diseases
/ virology
Pregnancy Complications, Infectious
/ virology
Brazil
Infant, Newborn
Autism Spectrum Disorder
/ virology
Child
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
03 Aug 2024
03 Aug 2024
Historique:
received:
01
12
2023
accepted:
18
06
2024
medline:
4
8
2024
pubmed:
4
8
2024
entrez:
3
8
2024
Statut:
epublish
Résumé
Zika virus (ZIKV) infection was first reported in 2015 in Brazil as causing microcephaly and other developmental abnormalities in newborns, leading to the identification of Congenital Zika Syndrome (CZS). Viral infections have been considered an environmental risk factor for neurodevelopmental disorders outcome, such as Autism Spectrum Disorder (ASD). Moreover, not only the infection per se, but maternal immune system activation during pregnancy, has been linked to fetal neurodevelopmental disorders. To understand the impact of ZIKV vertical infection on brain development, we derived induced pluripotent stem cells (iPSC) from Brazilian children born with CZS, some of the patients also being diagnosed with ASD. Comparing iPSC-derived neurons from CZS with a control group, we found lower levels of pre- and postsynaptic proteins and reduced functional synapses by puncta co-localization. Furthermore, neurons and astrocytes derived from the CZS group showed decreased glutamate levels. Additionally, the CZS group exhibited elevated levels of cytokine production, one of which being IL-6, already associated with the ASD phenotype. These preliminary findings suggest that ZIKV vertical infection may cause long-lasting disruptions in brain development during fetal stages, even in the absence of the virus after birth. These disruptions could contribute to neurodevelopmental disorders manifestations such as ASD. Our study contributes with novel knowledge of the CZS outcomes and paves the way for clinical validation and the development of potential interventions to mitigate the impact of ZIKV vertical infection on neurodevelopment.
Identifiants
pubmed: 39097642
doi: 10.1038/s41598-024-65392-8
pii: 10.1038/s41598-024-65392-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
18002Informations de copyright
© 2024. The Author(s).
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