Study demonstrates the interaction between Zika virus and saxitoxin in human brain development

In recent years, the Zika virus (ZIKV) epidemic that affected Brazil, particularly the Northeast region, drew attention due to cases of microcephaly and other congenital malformations, known as Congenital Zika Syndrome. The high incidence of severe cases in specific regions raised the hypothesis that environmental factors could be exacerbating the effects of the virus. A new study published in Scientific Reports and conducted by researchers from the D’Or Institute for Research and Education (IDOR) in partnership with the Federal University of Rio de Janeiro (UFRJ) has revealed the role of saxitoxin (STX), a neurotoxin found in water reservoirs contaminated by cyanobacteria, in increasing neuronal damage caused by ZIKV.

"The years 2015 and 2016 were marked by intense drought in the Northeast, reducing water levels in reservoirs intended for human consumption. These conditions favored the proliferation of cyanobacteria, which release neurotoxins into the water, such as saxitoxin. Previous studies by the IDOR team had already indicated that saxitoxin in these reservoirs could exacerbate Zika virus infection in human brain organoids. However, it was not yet clear how this neurotoxin acted or which brain cells were most affected," explains Dr. Marília Zaluar, a neuroscientist at IDOR and one of the study’s coordinators.

To analyze the relationship between ZIKV and STX in different types of human brain cells, the researchers used organoid models known as "mini-brains." These structures are developed in the laboratory from pluripotent stem cells, which have the ability to differentiate into various cell types, such as cortical cells and sensory neurons.

The interaction between ZIKV and the neurotoxin was found to be more intense in both mature and immature neuronal cells, whereas other nervous system cell groups showed greater resistance to the combined damage.

The researchers also observed that STX has the ability to block the spontaneous electrical activity of neurons. Electrical activity is fundamental for brain development, as neuronal activity synchronization is essential for the formation of connections between neurons. In the experiments, it was demonstrated that after the removal of saxitoxin, neurons were able to partially recover their electrical activity, but many had already suffered irreversible cellular damage.

Another key finding was the confirmation that STX intensifies viral infection, suggesting that saxitoxin not only increases neuronal vulnerability to cell death but also facilitates viral replication.

Human exposure to saxitoxin may be a key factor in explaining the higher severity and significantly greater frequency of Congenital Zika Syndrome cases in Northeast Brazil compared to other regions of the country. With these results, the researchers have opened new avenues for investigating the combined impact of environmental and infectious factors on human neurological development, a field that still lacks in-depth studies.

The research reinforces the importance of monitoring and controlling the presence of cyanobacteria and their toxins in water reservoirs, especially in drought-prone regions. This need becomes even more critical in the current reality of climate change, in which extreme events such as severe droughts are expected to occur more frequently.