Mechanism of Bisphenol F Affecting Motor System and Motor Activity in Zebrafish

Abstract

Bisphenol F (BPF; 4,4′-dihydroxydiphenylmethane) is one of the most frequently used compounds in the manufacture of plastics and epoxy resins. Previous studies have demonstrated that BPF affects locomotor behavior, oxidative stress, and neurodevelopment in zebrafish. However, its neurotoxic effects are controversial, and the underlying mechanisms are unclear. In order to determine whether BPF affects the motor system, we exposed zebrafish embryos to BPF and assessed behavioral, histological, and neurochemical changes. Spontaneous locomotor behavior and startle response were significantly decreased in BPF-treated zebrafish larvae compared with control larvae. BPF induced motor degeneration and myelination defects in zebrafish larvae. In addition, embryonic exposure to BPF resulted in altered metabolic profiles of neurochemicals, including neurotransmitters and neurosteroids, which may impact locomotion and motor function. In conclusion, exposure to BPF has the potential to affect survival, motor axon length, locomotor activity, myelination, and neurochemical levels of zebrafish larvae.

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“…Changes in specific ion channel expression in the brain have also been found [73]. Further evidence suggests alterations to the hypothalamus-pituitary-thyroid (HPT) [79,85,87] and HP-gonadal (HPG) [81,85,96,97] axes, circadian rhythms [91], and the visual system [90,95,98]. Similar to the behavioral results discussed above, BPAF seems to most severely alter genes and hormones compared to BPB, BPS, and BPF [81].…”

“…Instances of social behavior decreased following perinatal exposure to BPAF, BPAP, BPB, BPC, BPF, BPS, and HPP [73,89]. Studies also suggest deficits in learning and memory (BPS) [88] and response to stimuli (BPF, BPS) [87,90].…”

“…Embryonic and larval BPA analogue exposure has neurotoxic effects in zebrafish (Table 2). In general, embryonic and larval exposure to bisphenols decreases embryo spontaneous movement and larvae locomotion [26,74,[79][80][81][82][83][84][85][86][87], with the exception of BPS, which produced mixed results. According to multiple comparison studies, BPAF leads to the most severe alterations in locomotion, followed by BPF, which is similar to BPA, and then BPS [80,81].…”

“…According to multiple comparison studies, BPAF leads to the most severe alterations in locomotion, followed by BPF, which is similar to BPA, and then BPS [80,81]. Open-field test results did not show consistent results [74,87,88]. Instances of social behavior decreased following perinatal exposure to BPAF, BPAP, BPB, BPC, BPF, BPS, and HPP [73,89].…”

“…It is clear from the zebrafish studies that exposure to many BPA analogues leads to disrupted neuronal development, with immunohistochemistry and gene expression studies demonstrating decreased motor neuron lengths [80,87,91,92], alterations in neuron differentiation [79,93,94], neurogenesis [26,73,80,83,95], and neural maturation [93], in addition to a rise in brain degeneration [85] and neuron apoptosis [86]. Specific neurotransmitters including GABA, glutamine, glutamate, dopamine, serotonin, acetylcholine, and isotocin (oxytocin-family peptide) also show changes with perinatal analogue exposure [26,80,87,88]. Changes in specific ion channel expression in the brain have also been found [73].…”