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Zika virus-induced hyper excitation precedes death of mouse primary neuron

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journal contribution
posted on 2018-04-27, 00:00 authored by Julie Gaburro, Asim BhattiAsim Bhatti, Vinod SundaramoorthyVinod Sundaramoorthy, M Dearnley, D Green, Saeid Nahavandi, P N Paradkar, J B Duchmin
Background
Zika virus infection in new born is linked to congenital syndromes, especially microcephaly. Studies have shown that these neuropathies are the result of significant death of neuronal progenitor cells in the central nervous system of the embryo, targeted by the virus. Although cell death via apoptosis is well acknowledged, little is known about possible pathogenic cellular mechanisms triggering cell death in neurons.

Methods
We used in vitro embryonic mouse primary neuron cultures to study possible upstream cellular mechanisms of cell death. Neuronal networks were grown on microelectrode array and electrical activity was recorded at different times post Zika virus infection. In addition to this method, we used confocal microscopy and Q-PCR techniques to observe morphological and molecular changes after infection.

Results
Zika virus infection of mouse primary neurons triggers an early spiking excitation of neuron cultures, followed by dramatic loss of this activity. Using NMDA receptor antagonist, we show that this excitotoxicity mechanism, likely via glutamate, could also contribute to the observed nervous system defects in human embryos and could open new perspective regarding the causes of adult neuropathies.

Conclusions
This model of excitotoxicity, in the context of neurotropic virus infection, highlights the significance of neuronal activity recording with microelectrode array and possibility of more than one lethal mechanism after Zika virus infection in the nervous system.

History

Journal

Virology journal

Volume

15

Article number

79

Pagination

1 - 13

Publisher

BioMed Central

Location

London, Eng.

ISSN

1743-422X

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2018, The Authors