Fluoride exposure causes behavioral, molecular and physiological changes in adult zebrafish (Danio rerio) and their offspring.

ABSTRACT

Fluoride exposure through drinking water, foods, cosmetics, and drugs causes genotoxic effects, oxidative damage, and impaired cognitive abilities. In our study, the effects of fluoride on anxiety caused by the circadian clock and circadian clock changes in a zebrafish model were investigated at the molecular level on parents and the next generations. For this purpose, adult zebrafish were exposed to 1.5 ppm, 5 ppm, and 100 ppm fluoride for 6 weeks. At the end of exposure, anxiety-like behaviors and sleep/wake behaviors of the parent fish were evaluated with the circadian rhythm test and the novel tank test. In addition, antioxidant enzyme activities and melatonin levels in brain tissues were measured. In addition, morphological, physiological, molecular and behavioral analyzes of offspring taken from zebrafish exposed to fluoride were performed. In addition, histopathological analyzes were made in the brain tissues of both adult zebrafish and offspring, and the damage caused by fluoride was determined. The levels of BMAL1, CLOCK, PER2, GNAT2, BDNF and CRH proteins were measured by immunohistochemical analysis and significant changes in their levels were determined in the F- treated groups. The data obtained as a result of behavioral and molecular analyzes showed that parental fluoride exposure disrupts the circadian rhythm, causes anxiety-like behaviors, and decreases the levels of brain antioxidant enzymes and melatonin in parents. In addition, delay in hatching, increase in death and body malformations, and decrease in blood flow velocity, and locomotor activity was observed in parallel with dose increase in offspring. On the other hand, an increase in offspring apoptosis rate, ROS level, and lipid accumulation was detected. As a result, negative effects of fluoride exposure on both parents and next generations have been identified.