Sunday, July 4, 2021

Per- and Polyfluoroalkyl Substances (PFAS) are a class of global toxicants that are resistant to environmental degradation. Exposure to perfluorooctane sulfonate (PFOS), a prevalent PFAS congener, dampens adaptive immune responses in children. However, it is not known whether PFOS exposure affects the development and function of microglia, the resident innate immune cells in the brain. Using a single cell image analysis pipeline, we found that PFOS exposure produced a rounded, activated microglia morphology in developing zebrafish. PFOS-exposed embryos exhibited a heightened microglial response to brain injury. The exacerbated responses were not due to changes in inflammatory cytokine signaling or an increase in cell death; therefore, we examined other factors in the microenvironment that may modulate microglial development and behavior. Using the photoconvertible calcium indicator CaMPARI, we observed increased neural activity following PFOS exposure. The observed increase may reflect aberrant connectivity associated with the failure of microglia to refine neural networks. Alternatively, the increase in neuronal firing may drive the observed activated microglial phenotypes and alter microglial response to injury. Using optogenetics, we were able to induce a ramified, less activated state in microglia and rescue the exacerbated microglial response to brain injury. We are currently conducting experiments to determine if neural silencing is sufficient to rescue the altered microglial morphology in PFOS-exposed embryos and the microglial response to brain injury.