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Fundamental neurochemistry review: Glutamatergic dysfunction as a central mechanism underlying flavivirus‐induced neurological damage

Abstract The Flaviviridae family comprises positive‐sense single‐strand RNA viruses mainly transmitted by arthropods. Many of these pathogens are especially deleterious to the nervous system, and a myriad of neurological symptoms have been associated with infections by Zika virus (ZIKV), West Nile v...

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Bibliographic Details
Published in:Journal of neurochemistry 2023-09, Vol.166 (6), p.915-927
Main Authors: Nogueira, Clara O., Rocha, Tamires, Messor, Daniel F., Souza, Isis N. O., Clarke, Julia R.
Format: Article
Language:English
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Summary:Abstract The Flaviviridae family comprises positive‐sense single‐strand RNA viruses mainly transmitted by arthropods. Many of these pathogens are especially deleterious to the nervous system, and a myriad of neurological symptoms have been associated with infections by Zika virus (ZIKV), West Nile virus (WNV), and Japanese encephalitis virus (JEV) in humans. Studies suggest that viral replication in neural cells and the massive release of pro‐inflammatory mediators lead to morphological alterations of synaptic spine structure and changes in the balance of excitatory/inhibitory neurotransmitters and receptors. Glutamate is the predominant excitatory neurotransmitter in the brain, and studies propose that either enhanced release or impaired uptake of this amino acid contribute s to brain damage in several conditions. Here, we review existing evidence suggesting that glutamatergic dysfunction ‐ induced by flaviviruses is a central mechanism for neurological damage and clinical outcomes of infection. We also discuss current data suggesting that pharmacological approaches that counteract glutamatergic dysfunction show benefits in animal models of such viral diseases. image
ISSN:0022-3042
1471-4159
1471-4159
DOI:10.1111/jnc.15935