Zebrafish is a predictive model for identifying compounds that protect against brain toxicity in severe acute organophosphorus intoxication

Faria, Melissa; Prats, Eva; Padrós, Francesc; Soares, Amadeu M.V.M.; Raldúa, Demetrio

doi:10.1007/s00204-016-1851-3

Cited by 23 publications

(9 citation statements)

References 49 publications

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“…Appropriate primers for the ten selected genes ( gap43 , gfap , mbpa , nsfa , opn1lw1 , opn1mw1 , tuba1b , syn2a , syt1a , sytxbp1b ) were designed using Primer Express 2.0 software (Applied Biosystems, Foster City, CA) and the Primer-Blast server ( http://www.ncbi.nlm.nih.gov/tools/primer-blast ; primer sequences in Table S2 ) and synthesized by Sigma. House-keeping gene ppia2 was selected as reference gene 56 .…”

Section: Methodsmentioning

confidence: 99%

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Modelling acrylamide acute neurotoxicity in zebrafish larvae

Prats

Gómez‐Canela

Ben-Lulu

et al. 2017

Sci Rep

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Acrylamide (ACR), a type-2 alkene, may lead to a synaptopathy characterized by ataxia, skeletal muscles weakness and numbness of the extremities in exposed human and laboratory animals. Currently, only the mildly affected patients undergo complete recovery, and identification of new molecules with therapeutic bioactivity against ACR acute neurotoxicity is urgently needed. Here, we have generated a zebrafish model for ACR neurotoxicity by exposing 5 days post-fertilization zebrafish larvae to 1 mM ACR for 3 days. Our results show that zebrafish mimics most of the pathophysiological processes described in humans and mammalian models. Motor function was altered, and specific effects were found on the presynaptic nerve terminals at the neuromuscular junction level, but not on the axonal tracts or myelin sheath integrity. Transcriptional markers of proteins involved in synaptic vesicle cycle were selectively altered, and the proteomic analysis showed that ACR-adducts were formed on cysteine residues of some synaptic proteins. Finally, analysis of neurotransmitters profile showed a significant effect on cholinergic and dopaminergic systems. These data support the suitability of the developed zebrafish model for screening of molecules with therapeutic value against this toxic neuropathy.

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Section: Methodsmentioning

confidence: 99%

“…Changes in mRNA abundance in samples from different treatments were calculated by the ΔΔCp method 56 , using corrected Cp values from treated and non-treated samples Eq. ( 2 ) …”

Section: Methodsmentioning

confidence: 99%

Modelling acrylamide acute neurotoxicity in zebrafish larvae

Prats

Gómez‐Canela

Ben-Lulu

et al. 2017

Sci Rep

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“…Zebrafish is a cyprinid increasingly used as a vertebrate model for the study of the molecular mechanisms of brain function (Babin et al, 2014;Faria et al, 2017;Gómez-Canela et al, 2018), with the key advantage of being suitable for in vivo high-throughput screening of chemical libraries for pharmacological and/or toxicological effects. An assay to assess short-term habituation in zebrafish larvae, based on determining the motor activity of the larvae after the delivery of repetitive acoustic stimuli, was recently developed (Best et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Development of a vibrational startle response assay for screening environmental pollutants and drugs impairing predator avoidance

Faria

Prats

Novoa-Luna

et al. 2019

Science of The Total Environment

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The present paper describes the Vibrational Startle Response Assay (VSRA), a new robust, simple and automated in vivo medium-to high-throughput procedure for assessment of the escape response and its habituation in zebrafish larvae. Such behaviors enable fish larvae to escape from predator strikes in aquatic ecosystems. The assay is based on measuring the distance moved by each larva during the startle response evoked by repetitive vibrational stimuli. The iterative reduction observed in the response to a series of tapping stimulus in VSRA met the main criteria of habituation. Subsequently, the analysis of concordance using a battery of neuroactive compounds modulating different neurotransmitter systems demonstrated that the results of VSRA are highly predictive of the effects on other vertebrates. Finally, as a proof of concept, VSRA was used to test two relevant environmental pollutants at different concentrations. The results demonstrated that VSRA is suitable for concentration-response analysis of environmental pollutants, opening the possibility to determine the potency and the associated hazard of impaired escape response for the different compounds. Therefore, we suggest that VSRA could be a valuable tool for screening of chemical compounds capable of compromising predator avoidance behavior.

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“…In addition, due to the large space requirement and relatively expensive instrumental setting, the assessment of ecotoxicity by multiple behavioral endpoints using mice has not yet been widely explored. To overcome these limitations, zebrafish have been proposed to serve as an alternative lower vertebrate model for ecotoxicity research.The use of zebrafish (Danio rerio) has several advantages over rodent models, such as easy maintenance, prolific breeding, rapid development, and external development, making them a practical and robust animal model for human diseases and developmental and toxicological studies [11,[18][19][20][21]. Several studies have demonstrated the neurotoxic effects of lead exposure at early embryonic stages, thereby causing some changes in the development of the nervous system.…”

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Chronic Exposure to Low Concentration Lead Chloride-Induced Anxiety and Loss of Aggression and Memory in Zebrafish

Thi

Audira

et al. 2020

IJMS

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Lead and lead-derived compounds have been extensively utilized in industry, and their chronic toxicity towards aquatic animals has not been thoroughly addressed at a behavioral level. In this study, we assessed the risk of exposure to lead at a waterborne environmental concentration in adult zebrafish by behavioral and biochemical analyses. Nine tests, including three-dimension (3D) locomotion, novel tank exploration, mirror biting, predator avoidance, social interaction, shoaling, circadian rhythm locomotor activity, color preference, and a short-term memory test, were performed to assess the behavior of adult zebrafish after the exposure to 50 ppb PbCl 2 for one month. The brain tissues were dissected and subjected to biochemical assays to measure the relative expression of stress biomarkers and neurotransmitters to elucidate the underlying mechanisms for behavioral alterations. The results of the behavioral tests showed that chronic exposure to lead could elevate the stress and anxiety levels characterized by elevated freezing and reduced exploratory behaviors. The chronic exposure to PbCl 2 at a low concentration also induced a sharp reduction of aggressiveness and short-term memory. However, no significant change was found in predator avoidance, social interaction, shoaling, or color preference. The biochemical assays showed elevated cortisol and reduced serotonin and melatonin levels in the brain, thus, altering the behavior of the PbCl 2 -exposed zebrafish. In general, this study determined the potential ecotoxicity of long-term lead exposure in adult zebrafish through multiple behavioral assessments. The significant findings were that even at a low concentration, long-term exposure to lead could impair the memory and cause a decrease in the aggressiveness and exploratory activities of zebrafish, which may reduce their survival fitness.(EC10/NOEC-usually more than 14 days) on fish range from 18 to 1559 µg/L and 44 to 437 µg/L, respectively [3,4].More evidence has shown the detrimental impacts of lead on human health, especially at a neurobehavioral level. The neurotoxicity of chronic exposure to low concentrations of lead can impair cognitive performance in childhood through to adulthood [5][6][7][8][9]. Some studies demonstrated the correlation between the exposure to lead at low concentrations and attention-deficit/hyperactivity disorder (ADHD) in children [10]. The development of the central nervous system can be disrupted when children are exposed to low concentrations of lead for a long period of time (blood lead level below 10 mg/dL) [11]. Therefore, lead toxicity has become a serious issue for human health and environmental protection [6]. According to previous studies, the effect of lead on the nervous system includes the disruption of key molecules during neuronal migration and differentiation, interference with synapse formation mediated by a reduction in neuronal sialic acid production and premature differentiation of glial cells, interference with neurotransmitter release, and disruption of the...

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Zebrafish is a predictive model for identifying compounds that protect against brain toxicity in severe acute organophosphorus intoxication

Cited by 23 publications

References 49 publications

Modelling acrylamide acute neurotoxicity in zebrafish larvae

Modelling acrylamide acute neurotoxicity in zebrafish larvae

Development of a vibrational startle response assay for screening environmental pollutants and drugs impairing predator avoidance

Chronic Exposure to Low Concentration Lead Chloride-Induced Anxiety and Loss of Aggression and Memory in Zebrafish

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