Acute exposure to DE‐71: Effects on locomotor behavior and developmental neurotoxicity in zebrafish larvae

Abstract

Abstract-The aim of the present study was to investigate the acute developmental neurotoxicity of polybrominated diphenyl ethers (PBDEs) in zebrafish larvae. From 2 to 120 h postfertilization zebrafish embryos were exposed to 31.0, 68.7, and 227.6 mg/L). The authors studied the locomotor behavior of larvae, involvement of the cholinergic system, and selected gene and protein expressions in the central nervous system. The results showed that low DE-71 concentration caused hyperactivity, whereas higher concentrations decreased activity during the dark period. During the light period, larval activity was significantly reduced in a concentration-dependent manner. In the cholinergic system, acetylcholinesterase activity significantly increased (10.7 and 12.4%) in the 68.7 and 227.6 mg/L exposure groups, respectively, and acetylcholine concentration accordingly decreased (60.5%) in the 227.6 mg/L exposure group. The mRNA expressions of genes encoding myelin basic protein, neuron microtubule protein (a1-tubulin), and sonic hedgehog a were significantly downregulated. Western blotting assay demonstrated that the protein concentration of a1-tubulin was also decreased.Overall, the present study demonstrated that acute exposure to PBDEs can disrupt the neurobehavior of zebrafish larvae and affect cholinergic neurotransmission and neuron development. Environ. Toxicol. Chem. 2012;31:233831: -234431: . # 2012

Zebrafish as a Model for Developmental Neurotoxicity Assessment: The Application of the Zebrafish in Defining the Effects of Arsenic, Methylmercury, or Lead on Early Neurodevelopment

“…Zebrafish studies have revealed the neurotoxic effects of exposure to PBDEs (e.g., DE-71, BDE-47, BDE-49), showing alteration in neurobehavior, genetic expression, cholinergic system and/or axonal growth [39][40][41]52]. As an example, in Chen et al [39], zebrafish (120 hpf) developmentally exposed to DE-71 exhibited altered locomotor movement, increased AChE activity, and decreased expression of nervous system genes (myelin basic protein, α1-tubulin, and sonic hedgehog a).…”

“…As an example, in Chen et al [39], zebrafish (120 hpf) developmentally exposed to DE-71 exhibited altered locomotor movement, increased AChE activity, and decreased expression of nervous system genes (myelin basic protein, α1-tubulin, and sonic hedgehog a). Parental exposure to DE-71 (for 150 days) also induced changes in neurobehavior, CNS gene expression (myelin basic protein, synapsin IIa, α1-tubulin), and the cholinergic system but with decreased AChE activity in F 1 offspring at 96 hpf [40].…”

PBDE flame retardants

“…Specifically, neurodevelopmental abnormalities, including impaired normal motor behavior and inhibited neuron growth and differentiation, as well as morphological deformities have been measured in zebrafish larvae exposed to: PentaBDE 157,197,198 ; a mixture of BDE-47, -99, -100, -153, and -183 199 ; BDE-47, [200][201][202][203] BDE-49 204 ; and BDE-209 205 ( Table 5).…”

“…In another study by this same research group, the PentaBDE commercial mixture also caused a downregulation in mRNA transcript abundances of sonic hedgehog (Shh). 197 This suggests a possible contributory role for thyroid dysregulation in some PBDE related neurodevelopmental toxicity as the Shh pathway, as well as its coreceptors patched (Ptc) and smoothened (Smo), have been shown to be regulated by THs in embryonic forebrain signaling and development in mammals. 206 Only one study has examined neurotoxicity endpoints in a fish species beyond zebrafish.…”

Literature review on in vitro and alternative Developmental Neurotoxicity (DNT) testing methods

“…Examples are given in Table 50 where exposure to DNT positive compounds disrupts the neurobehavior of zebrafish larvae and affect cholinergic neurotransmission. In work by Chen et al (2012a) it is shown that low DE-71 concentration caused hyperactivity, whereas higher concentrations decreased activity during the dark period. During the light period, larval activity was significantly reduced in a concentration-dependent manner.…”