Calcium signaling as a possible mechanism behind increased locomotorresponse in zebrafish larvae exposed to a human relevant persistent organicpollutant mixture or PFOS

Persistent organic pollutants (POPs) are widespread in the environment and their bioaccumulation can lead toadverse health effects in many organisms. Previously, using zebrafish as a model vertebrate, we found larvaeexposed to a mixture of 29 POPs based on average blood levels from the Scandinavian population showedhyperactivity, and identified perfluorooctanesulfonic acid (PFOS) as the driving agent for the behavioralchanges. In order to identify possible mechanisms, we exposed zebrafish larvae from 6 to 96 h post fertilizationto the same mixture of POPs in two concentrations or a single PFOS exposure (0.55 and 3.83μM) and performedbehavioral tests and transcriptomics analysis. Behavioral alterations of exposed zebrafish larvae included hy-peractivity and confirmed previously reported results. Transcriptomics analysis showed upregulation of tran-scripts related to muscle contraction that is highly regulated by the availability of calcium in the sarcoplasmicreticulum. Ingenuity pathway analysis showed that one of the affected pathways in larvae exposed to the POPmixture and PFOS was calcium signaling via the activation of the ryanodine receptors (RyR). Functional analyseswith RyR inhibitors and behavioral outcomes substantiate thesefindings. Additional pathways affected wererelated to lipid metabolism in larvae exposed to the lower concentration of PFOS. By using omics technology, weobserved that the altered behavioral pattern in exposed zebrafish larvae may be controlled directly by me-chanisms affecting muscle function rather than via mechanisms connected to neurotoxicity.