Saxitoxin potentiates Zika virus-induced cell death in human neurons but not in neural progenitors and astrocytes

Abstract

The Zika virus (ZIKV) outbreak in Brazil between 2015 and 2016 was associated with an increased prevalence of severe congenital malformations, including microcephaly. Notably, the distribution of microcephaly cases was not uniform across the country, with a disproportionately higher incidence recorded in the Northeast region (NE). Our previous work demonstrated that saxitoxin (STX), a toxin ubiquitously present in the drinking water reservoirs of the NE, exacerbated the damaging effects of ZIKV on the developing brain. In the present study, we hypothesized that STXs impact might vary among different neural cell types. Our experimental observations suggest that exposure to STX potentiates the neurotoxic effect of Zika Virus (ZIKV) on human neuronal cells. However, while ZIKV infection demonstrated severe impacts on astrocytes and neural stem cells (NSCs), the addition of STX did not exacerbate these effects. We observed that neurons subjected to STX exposure were more prone to apoptosis and displayed a higher number of ZIKV-infected cells. These findings suggest that STX exacerbates the harmful effects of ZIKV on neurons, thereby providing a plausible explanation for the heightened severity of ZIKV-induced congenital malformations observed in Brazils NE. This study underscores the importance of understanding the interactive effects of environmental toxins and infectious pathogens on neural development, with potential implications for public health policies and interventions.