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Zika Virus-Mediated Death of Hippocampal Neurons Is Independent From Maturation State

Zika virus (ZIKV) infection of pregnant women and diaplazental transmission to the fetus is linked to the congenital syndrome of microcephaly in newborns. This neuropathology is believed to result from significant death of neuronal progenitor cells (NPC). Here, we examined the fate of neurons in the...

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Autores principales: Büttner, Caroline, Heer, Maxi, Traichel, Jasmin, Schwemmle, Martin, Heimrich, Bernd
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736629/
https://www.ncbi.nlm.nih.gov/pubmed/31551711
http://dx.doi.org/10.3389/fncel.2019.00389
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author Büttner, Caroline
Heer, Maxi
Traichel, Jasmin
Schwemmle, Martin
Heimrich, Bernd
author_facet Büttner, Caroline
Heer, Maxi
Traichel, Jasmin
Schwemmle, Martin
Heimrich, Bernd
author_sort Büttner, Caroline
collection PubMed
description Zika virus (ZIKV) infection of pregnant women and diaplazental transmission to the fetus is linked to the congenital syndrome of microcephaly in newborns. This neuropathology is believed to result from significant death of neuronal progenitor cells (NPC). Here, we examined the fate of neurons in the developing hippocampus, a brain structure which houses neuronal populations of different maturation states. For this purpose, we infected hippocampal slice cultures from immunocompetent newborn mice with ZIKV and monitored changes in hippocampal architecture. In neurons of all hippocampal subfields ZIKV was detected by immunofluorescence labeling and electron microscopy. This includes pyramidal neurons that maturate during the embryonic phase. In the dentate gyrus, ZIKV could be found in the Cajal–Retzius (CR) cells which belong to the earliest born cortical neurons, but also in granule cells that are predominantly generated postnatally. Intriguingly, virus particles were also present in the correctly outgrowing mossy fiber axons of juvenile granule cells, suggesting that viral infection does not impair region- and layer-specific formation of this projection. ZIKV infection of hippocampal tissue was accompanied by both a profound astrocyte reaction indicating tissue injury and a microglia response suggesting phagocytotic activity. Furthermore, depending on the viral load and incubation time, we observed extensive overall neuronal loss in the cultured hippocampal slice cultures. Thus, we conclude ZIKV can replicate in various neuronal populations and trigger neuronal death independent of the maturation state of infected cells.
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spelling pubmed-67366292019-09-24 Zika Virus-Mediated Death of Hippocampal Neurons Is Independent From Maturation State Büttner, Caroline Heer, Maxi Traichel, Jasmin Schwemmle, Martin Heimrich, Bernd Front Cell Neurosci Neuroscience Zika virus (ZIKV) infection of pregnant women and diaplazental transmission to the fetus is linked to the congenital syndrome of microcephaly in newborns. This neuropathology is believed to result from significant death of neuronal progenitor cells (NPC). Here, we examined the fate of neurons in the developing hippocampus, a brain structure which houses neuronal populations of different maturation states. For this purpose, we infected hippocampal slice cultures from immunocompetent newborn mice with ZIKV and monitored changes in hippocampal architecture. In neurons of all hippocampal subfields ZIKV was detected by immunofluorescence labeling and electron microscopy. This includes pyramidal neurons that maturate during the embryonic phase. In the dentate gyrus, ZIKV could be found in the Cajal–Retzius (CR) cells which belong to the earliest born cortical neurons, but also in granule cells that are predominantly generated postnatally. Intriguingly, virus particles were also present in the correctly outgrowing mossy fiber axons of juvenile granule cells, suggesting that viral infection does not impair region- and layer-specific formation of this projection. ZIKV infection of hippocampal tissue was accompanied by both a profound astrocyte reaction indicating tissue injury and a microglia response suggesting phagocytotic activity. Furthermore, depending on the viral load and incubation time, we observed extensive overall neuronal loss in the cultured hippocampal slice cultures. Thus, we conclude ZIKV can replicate in various neuronal populations and trigger neuronal death independent of the maturation state of infected cells. Frontiers Media S.A. 2019-08-27 /pmc/articles/PMC6736629/ /pubmed/31551711 http://dx.doi.org/10.3389/fncel.2019.00389 Text en Copyright © 2019 Büttner, Heer, Traichel, Schwemmle and Heimrich. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Büttner, Caroline
Heer, Maxi
Traichel, Jasmin
Schwemmle, Martin
Heimrich, Bernd
Zika Virus-Mediated Death of Hippocampal Neurons Is Independent From Maturation State
title Zika Virus-Mediated Death of Hippocampal Neurons Is Independent From Maturation State
title_full Zika Virus-Mediated Death of Hippocampal Neurons Is Independent From Maturation State
title_fullStr Zika Virus-Mediated Death of Hippocampal Neurons Is Independent From Maturation State
title_full_unstemmed Zika Virus-Mediated Death of Hippocampal Neurons Is Independent From Maturation State
title_short Zika Virus-Mediated Death of Hippocampal Neurons Is Independent From Maturation State
title_sort zika virus-mediated death of hippocampal neurons is independent from maturation state
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736629/
https://www.ncbi.nlm.nih.gov/pubmed/31551711
http://dx.doi.org/10.3389/fncel.2019.00389
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