Toxicant induced behavioural aberrations in larval zebrafish are dependent on minor methodological alterations

Fraser, Thomas W.K.; Khezri, Abdolrahman; Herranz-Jusdado, J.G.; Lewandowska-Sabat, Anna; Henry, Theodore B.; Ropstad, Erik

doi:10.1016/j.toxlet.2017.05.021

Cited by 43 publications

(39 citation statements)

References 24 publications

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“…These findings are corroborated by De Esch et al [27], who compared 5-, 6-and 7-day-old embryos/larvae and Leuthold et al [68] who compared 4-and 5-day-old embryos. Fraser et al [38] reported increased movement for older embryos (120 > 100 > 96 hpf ) when raised in constant darkness. In contrast, Ingebretson and Masino [50], while considering total distance moved in constant light, reported that 7-day-old larvae moved less than 4-day-old embryos.…”

Section: Biological (Intrinsic) Factors Developmental Stagementioning

confidence: 98%

“…In some studies, the differentiation between hypo-and hyperactivity has been suggested as a potential indicator for neuroactivity MoA [31,38,60]. With respect to embryonic behavior of unexposed embryos, hypoactivity refers to a decrease in the spontaneous or induced movement of embryos, while hyperactivity refers to the opposite.…”

Section: The Use Of Hypo-and Hyperactivity As a Predictormentioning

confidence: 99%

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Hypo- or hyperactivity of zebrafish embryos provoked by neuroactive substances: a review on how experimental parameters impact the predictability of behavior changes

et al. 2019

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Tests with zebrafish embryos have gained wide acceptance as an alternative test model for drug development and toxicity testing. In particular, the behavioral response of the zebrafish embryo is currently seen as a useful endpoint to diagnose neuroactive substances. Consequently, several behavioral test methods have been developed addressing various behavioral endpoints such as spontaneous tail coiling (STC), photomotor response (PMR), locomotor response (LMR) and alternating light/dark-induced locomotor response (LMR-L/D). Although these methods are distinct in their application, most of their protocols differ quite strongly in the use of experimental parameters and this is usually driven by different research questions. However, if a single mode of action is to be diagnosed, then varying experimental parameters may cause incoherent behavioral responses (hypo-or hyperactivity) of zebrafish during toxicity assessment. This could lead to inconclusiveness of behavioral test results for use within a prospective and diagnostic risk assessment framework. To investigate the influence of these parameters, we conducted a review of existing behavioral assays to address the following two questions: (1) To what extent do varying experimental parameters influence observed effects in published behavioral test methods? (2) Is the observed behavior change (hypo-or hyperactivity) of zebrafish embryos consistent with the expected mode of action of a chemical? We compiled a set of 18 substances which are anticipated to be neuroactive. We found that behavioral changes are not only affected by chemicals but also variation in the use of experimental parameters across studies seems to have a high impact on the outcome and thus comparability between studies. Four parameters, i.e., exposure concentration, exposure duration, endpoint parameter and developmental stage were the most influential parameters. Varying combinations of these parameters caused a non-reproducible outcome for the hyperactivity expected for the organophosphates; chlorpyrifos and diazinon. We highlighted that the STC test shows a higher capacity to predict the hyperactivity of organophosphates, while PMR and LMR-L/D were more suitable to predict the hypoactivity expected for anticonvulsants. We provide a list of recommendations which, when implemented, may help to exclude the risk of bias due to experimental parameters if similar goals are desired.

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Section: Biological (Intrinsic) Factors Developmental Stagementioning

confidence: 98%

Section: The Use Of Hypo-and Hyperactivity As a Predictormentioning

confidence: 99%

Hypo- or hyperactivity of zebrafish embryos provoked by neuroactive substances: a review on how experimental parameters impact the predictability of behavior changes

et al. 2019

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“…In contrast, Chen et al (2016) found that zebrafish embryos exposure to 5 µM TBBPA altered larval behavior as evidenced by diminished activity bursts, lower speed of movement, motor deficits, delayed cranial motor neuron development, and inhibited primary motor neuron development. However, Fraser et al (2017) demonstrated that larval zebrafish behavioral responses to TBBPA were dependent on the photo-regime, larval age and arena size. It is of interest to note that the TBBPA-induced alteration in zebrafish behavior was associated with photomotor differences (Reif et al 2016) confirming that change in light and not TBBPA may be responsible for the observed behavioral alterations.…”

Section: Zebrafishmentioning

confidence: 99%

“…It has been reported that TBBPA affects thyroid hormone levels in zebrafish with consequent alterations in behavior suggesting that this organism may be utilized as a novel model to identify neurotoxic compounds (Fraser et al 2017;Zhu et al 2018;DeWit et al 2008). Alzualde et al (2018) reported no marked change in behavior and neurotoxic effects in larval zebrafish exposed to 1-100 µM TBBPA.…”

Section: Zebrafishmentioning

confidence: 99%

Absence of neurotoxicity and lack of neurobehavioral consequences due to exposure to tetrabromobisphenol A (TBBPA) exposure in humans, animals and zebrafish

Kacew

Hayes

2019

Arch Toxicol

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Tetrabromobisphenol A (2,2′,6,6′-tetrabromo-4,4′-isopropylidenediphenol, CAS no. 79-94-7) (TBBPA) is an effective brominated flame retardant present in many consumer products whose effectiveness is attributable to its ability to retard flames and consequently save human lives. Toxicokinetic studies revealed that TBBPA when absorbed via the gastrointestinal tract is rapidly metabolized to glucuronide or sulfate metabolites which are rapidly eliminated by the kidney. TBBPA does not accumulate in the body and there is no evidence that the parent compound is present in the brain. Although this brominated flame retardant was detected in human breast milk and serum, there was no evidence that TBBPA reached the brain in in vivo animal studies as reflected by the absence of neuropathological, neurotoxic, or behavioral alterations indicating that the central nervous system is not a target tissue. These animal investigations were further supported by use of the larval/embryo observations that TBBPA did not produce behavioral changes in a larval/embryo zebrafish a model of chemical-induced neurotoxicity. Although some protein expressions were increased, deceased or not affected in the blood-brain barrier indicating no evidence that TBBPA entered the brain, the changes were contradictory, or gender related, and behavior was not affected supporting that this compound was not neurotoxic. Taken together, TBBPA does not appear to target the brain and is not considered as a neurotoxicant.

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“…Zebrafish larval behaviour was previously shown to be affected after exposure to various toxicants at the early embryonic stages (Nellore, 2015;Fraser et al, 2017). Here, behavioural changes resulting from a short duration early life exposure to UV were assessed 5 days post fertilization, and results showed that exposure to the two highest UVA doses resulted in a significant decrease in larval activity compared to the controls.…”

Section: Behaviourmentioning

confidence: 92%

Sub-lethal UV radiation during early life stages alters the behaviour, heart rate and oxidative stress parameters in zebrafish (Danio rerio)

Hurem

Fraser

Gomes

et al. 2018

Ecotoxicology and Environmental Safety

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Environmental UV radiation in sufficient doses, as a possible consequence of climate change, is potent enough to affect living organisms with different outcomes, depending on the exposure life stage. The aim of this project was to evaluate the potentially toxic effects of exposure to sub-lethal and environmentally relevant doses of UVA (9.4, 18. 7, 37.7 J/cm 2) and UVB radiation (0.013, 0.025, 0.076 J/cm 2) on the development and behaviour in early life stages (4.5-5.5 hours post fertilization, hpf) of the zebrafish (Danio rerio). The used doses were all below the median lethal dose (LD50) and caused no significant difference in survival, deformities, or hatching between exposed and control groups. Compared to controls, there were transient UVA and UVB exposure effects on heart rate, with dose dependent reductions at 50 hpf, and at 60 hpf for UVA only. The UVB exposure caused an increasing trend in reactive oxygen species (ROS) formation at the two highest doses, even though only significant at 120 hpf for the second highest dose. Both UVA and UVB caused an increasing trend in lipid peroxidation (LPO) at the highest doses tested at 72 hpf. Furthermore, UVA exposure led to significant reductions in larval movement following exposure to the two highest doses of UVA, i.e., reduction in the time spent active and the total distance moved compared to control at 100 hpf, while no effect on the swimming speed was observed. The lowest dose of UVA had no effect on behaviour. In contrast, the highest dose of UVB led to a possible increase in the time spent active and a slower average swimming speed although these effects were not significant (p = 0.07). The obtained results show that UV doses below LD50 levels are able to cause changes in the behaviour and physiological parameters of zebrafish larvae, as well as oxidative stress in the form of ROS formation and LPO. Further testing is necessary to assess how this type of radiation and the effects observed could affect fish population dynamics.

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Toxicant induced behavioural aberrations in larval zebrafish are dependent on minor methodological alterations

Cited by 43 publications

References 24 publications

Hypo- or hyperactivity of zebrafish embryos provoked by neuroactive substances: a review on how experimental parameters impact the predictability of behavior changes

Hypo- or hyperactivity of zebrafish embryos provoked by neuroactive substances: a review on how experimental parameters impact the predictability of behavior changes

Absence of neurotoxicity and lack of neurobehavioral consequences due to exposure to tetrabromobisphenol A (TBBPA) exposure in humans, animals and zebrafish

Sub-lethal UV radiation during early life stages alters the behaviour, heart rate and oxidative stress parameters in zebrafish (Danio rerio)

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