Postnatal Zika virus infection increases seizure susceptibility and disrupts cortical organization and GABAergic interneuron positioning in mice.

Abstract

Zika virus (ZIKV) infection during gestation causes fetal brain abnormalities such as microcephaly, cortical malformations, and motor defects. Infected infants often develop epilepsy and other neurodevelopmental impairments later in life. Animal models show that ZIKV infection leads to seizures and neuroinflammation, disrupting brain development and function. While much research focuses on glutamatergic neuronal development, little is known about how ZIKV affects the development of GABAergic interneurons, which are crucial for brain circuitry and implicated in epilepsy. Here, we aim to evaluate the cortical GABAergic interneuron organization at the cerebral cortex during postnatal development until adulthood using a mouse model of ZIKV perinatal infection. ZIKV infection increases susceptibility to hyperthermic seizures in infected pups. Also, viral infection increases c-Fos, a marker of neuronal activity in the cerebral cortex, accompanied by cortical disorganization with dysmorphic cells observed in HE staining. Additionally, ZIKV disrupts the positioning of GABAergic interneurons, with a different distribution of calbindin-positive and parvalbumin-positive cells at P60 in infected mice, compared to the control. Taken together, these results suggest that ZIKV infection may contribute to impaired cortical inhibition and increased hyperthermic seizure risk.