Alterations in the Components of the GABA–Glutamate System During ZIKV Infection: A Neuroscience Approach

Zika virus (ZIKV) infection is associated with severe neurodevelopmental disorders. However, the molecular mechanisms involved in the imbalance of excitatory and inhibitory neurotransmitter systems remain poorly understood. In this study, we evaluated the expression of components of the GABA–glutamate system in neonatal BALB/c mice inoculated with ZIKV at 10 days post-infection (dpi). Analysis of GABA-A and NMDA receptors revealed widespread downregulation of GABA-A and NMDA receptor subunits in the cerebral cortex and cerebellum, except for the alpha-5 and epsilon GABA-A subunits, which were upregulated in the cerebellum. Infected mice also showed increased GABA immunoreactivity and glutamate loss. The enzymes involved in neurotransmitter synthesis or transport confirmed these findings when assessed by qRT-PCR or Western blot, revealing increased expression of GAD-65/67, accompanied by a loss of glutamate dehydrogenase (GLUD) in the cerebral cortex and cerebellum, along with decreased expression of the glutamate transporter (VGLUT) in the cerebral cortex. These findings suggest that GABA synthesis increases during ZIKV infection, creating a neurochemical environment that favors viral replication and contributes to the migration and synaptic defects observed in congenital Zika syndrome.