Bisphenol S Impairs Behaviors through Disturbing Endoplasmic Reticulum Function and Reducing Lipid Levels in the Brain of Zebrafish

Abstract

The number of neurotoxic pollutants is increasing, but their mechanism of action is unclear. Here, zebrafish were exposed to 0, 1, 10, and 100 μg/L bisphenol S (BPS) for different durations beginning at 2 h postfertilization (hpf) to explore the neurotoxic mechanisms of BPS. Zebrafish larvae exposed to BPS displayed abnormal neurobehaviors. At 48 and 120 hpf, BPS inhibited yolk lipid consumption and reduced the lipid distribution in the zebrafish brain. Moreover, BPS downregulated the mRNA levels of genes involved in fatty acid elongation in the endoplasmic reticulum (ER) and activated ER stress pathways at 48 and 120 hpf, and KEGG analysis after RNA-seq showed that the protein processing pathway in the ER was significantly enriched after BPS exposure. Exposure to ER toxicants (thapsigargin and tunicamycin), two positive controls, induced neurotoxic effects on zebrafish embryos and larvae similar to those of BPS exposure. These data suggested that BPS and ER toxicants disturbed ER function and reduced brain lipid levels. Continued exposure to BPS into adulthood not only inhibited brain fatty acid elongation and ER function but also caused abnormal swelling of the ER in zebrafish. Our data provide new insights into the neurotoxic mechanism of BPS.

Effects of Acute and Developmental Exposure to Bisphenol S on Chinese Medaka (Oryzias sinensis)

“…This analysis was consistent with the results of the embryos with enlarged yolk sacs in the BPS developmental exposure experiment. This phenomenon is also reflected in other instances where BPS was demonstrated to interfere with yolk lipid consumption in zebrafish embryos [ 65 ]. This result indicates that BPS exposure may cause harmful effects on energy metabolism.…”

Real-Time Monitoring of Tyrosine Hydroxylase Activity with a Ratiometric Fluorescent Probe

“…The Z -stack merged fluorescence of TH-1 and DTH-1 in different layers of the brain was observed, suggesting their good diffusion in the zebrafish brain. And we found that DTH-1 had a tendency to move toward the edge of brain near the yolk, which may be due to the high lipid content in this area . Because the clogP and logD 7.4 value of the DTH-1 are about 1.6 times those of TH-1 , DTH-1 has stronger lipid solubility (Figure and Figure S2B,C).…”

“…And we found that DTH-1 had a tendency to move toward the edge of brain near the yolk, which may be due to the high lipid content in this area. 57 Because the clogP and logD 7.4 value of the DTH-1 are about 1.6 times those of TH-1, DTH-1 has stronger lipid solubility (Figure 1 and Figure S2B,C).…”

Bis(2-ethylhexyl)-tetrabromophthalate Poses a Higher Exposure Risk and Induces Gender-Specific Metabolic Disruptions in Zebrafish Liver

“…TBPH exhibited a tendency to persist more in the brain and muscle, with longer half-lives in both female and male zebrafish. Several factors may contribute to the slower clearance rate of TBPH in brain tissue: (1) their high affinity for lipid tissues leads to accumulation in lipid-rich brain tissue over time, hindering clearance; (2) microcirculatory properties, such as slower cerebral blood flow and less dense blood vessels, contribute to prolonged retention of exposures; and (3) the presence of the blood–brain barrier presents a challenge for molecules to cross into or out of brain tissue, resulting in slower clearance rates …”