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

Physiological glutamatergic transmission and flavivirus-induced pathological alterations. On average, 400 million cases of infection by flaviviruses are reported every year. Several of these viruses may cause neurologic symptoms in a subset of patients. Here, we review studies that suggest that replication of neurotropic flavivirus causes massive release of pro-inflammatory mediators leading to increased release and compromised reuptake of glutamate, ultimately causing excitotoxicity, reactive oxygen species production, and cell death. We also discuss current data suggesting that pharmacological approaches that counteract glutamatergic dysfunction show benefits in animal models of such viral diseases. AbstractTheFlaviviridae 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 contributes to b...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: REVIEW Source Type: research