Neurodevelopmental low-dose bisphenol A exposure leads to early life-stage hyperactivity and learning deficits in adult zebrafish

Abstract

Developmental bisphenol A (BPA) exposure has been implicated in adverse behavior and learning deficits. The mode of action underlying these effects is unclear. The zebrafish model was employed to investigate the neurobehavioral effects of developmental bisphenol A (BPA) exposure. The objectives of this study were to identify whether low-dose, developmental BPA exposure affects larval zebrafish locomotor behavior and whether learning deficits occur in adults exposed during development. Two control compounds, 17β-estradiol (an estrogen receptor ligand) and GSK4716 (a synthetic estrogen related receptor gamma ligand), were included. Larval toxicity assays were used to determine appropriate BPA, 17β-estradiol, and GSK4716 concentrations for behavior testing. BPA tissue uptake was analyzed using HPLC and lower doses were extrapolated using a linear regression analysis. Larval behavior tests were conducted using a ViewPoint Zebrabox. Adult learning tests were conducted using a custom-built T-maze. BPA exposure to ≤30 μM was nonteratogenic in zebrafish. Neurodevelopmental BPA exposure to 0.01, 0.1, or 1 μM led to larval hyperactivity or learning deficits in adult zebrafish. Exposure to 0.1 μM 17β-estradiol or GSK4716 also led to larval hyperactivity. This study demonstrates the efficacy of using the larval zebrafish model for studying the neurobehavioral effects of low-dose developmental BPA exposure.

Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish

“…We also found that chronic BPA exposure (across 0-5 dpf) resulted in an inverted U-shaped hyperactivity dose-response curve (Fig. S1A), consistent with previous findings (32). Given that physiological responses to endocrine disruptors are known to be biphasic (10), with elevated responses at nanomolar concentrations, we next asked whether a lower dose of BPA also would cause hyperactive behavior.…”

“…1 B and C). Precedents in zebrafish demonstrate that this type of locomotor activity (i.e., hyperactivity burst) can be an indicator of anxiety-like behavior (32,33). We also found that chronic BPA exposure (across 0-5 dpf) resulted in an inverted U-shaped hyperactivity dose-response curve (Fig.…”

The zebrafish as a promising tool for modeling human brain disorders: A review based upon an IBNS Symposium

“…Similarly, there has also been a growing interest in characterizing non-social behaviors of zebrafish that may be related to social interaction and may allow better modeling of various human disorders (Seguin et al, 2016). Non-social behaviors that may influence social responses include locomotion, learning, anxiety, and fear responses (Al-Imari and Gerlai, 2008;Bencan et al, 2009;Lee et al, 2010;Maximino et al, 2010;Saili et al, 2012), but how these factors may influence social responses and how they may be regulated by social context remain unexplored.…”

Bisphenol A: Understanding Its Health Effects from the Studies Performed on Model Organisms

“…The authors also found that these efects are probably not due to an efect on estrogen receptors (or estrogen-like receptors) but may be due to its deleterious efects on the synthesis of key enzyme in steroid hormone synthesis, Aromatase B. This study also demonstrated that developmental BPA exposure led to larval hyperactivity or learning deicits in adult zebraish [90]. There are evidences for temperature-speciic impairment of swimming performance, disturbances in muscle activity and gene expression in zebraish due to exposure of BPA [91].…”