Neurobehavioral and metabolic consequences of embryonic triphenyl phosphate exposure across the lifespan in zebrafish.

Triphenyl phosphate (TPP) is a second-generation flame retardant which is wide-spread in the environment and persistent in the body. Early developmental exposure to TPP has been shown to cause significant neurobehavioral alterations that persist into adulthood. Questions remain concerning the neurobehavioral effects of developmental TPP exposure across the full lifespan and relevant mechanisms of long-term dysfunction. Using a zebrafish model, the current study examined the effects of TPP exposure during the first five days after fertilization on later life sensorimotor activity, emotional function, social response and mitochondrial energetics, specifically in late adulthood. Early developmental TPP exposure was found to cause locomotor hypoactivity in larvae. In the novel tank test TPP-induced hyperactivity was seen at 2.5 months and hypoactivity at 14 months. Correspondingly, the diving response only showed a subtle effect in this test, with TPP exposed 14-month old fish showing time dependent enhancements of the diving response. In the predator avoidance test, 8-month old fish showed greater avoidance of slow predator cues after developmental TPP exposure, but these fish no longer showed this pattern when tested at 14 months old. No significant effects of developmental TPP exposure were seen with tap startle response or shoaling behavior. TPP-induced decreased mitochondrial respiration was detected in the ovaries, but none of the other organs tested. This longitudinal study shows that early developmental TPP exposure is capable to producing neurobehavioral effects, but that those effects may be differentially expressed across development. These effects were not associated with mitochondrial and bioenergetic effects in the brain in late adulthood.