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Introduction
My current research interest is the understanding of the molecular bases of the neurotoxic effects of some environmental pollutants and drugs. By using zebrafish as vertebrate model, we try to identify the AOPs of neurotoxicants, by linking adverse effects from the molecular-initiating events to behavioural effects.
Additional affiliations
October 2009 - present
August 2004 - September 2009
July 2002 - August 2004
Publications
Publications (188)
The insecticide carbaryl is commonly found in indirectly exposed freshwater ecosystems at low concentrations considered safe for fish communities. In this study, we showed that after only 24 h of exposure to environmental concentrations of carbaryl (0.066-660 ng/L), zebrafish larvae exhibit impairments in essential behaviours. Interestingly, the ob...
N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-quinone) is a degradation product of 6PPD, an antioxidant widely used in rubber tires. 6PPD-quinone enters aquatic ecosystems through urban stormwater runoff and has been identified as the chemical behind the urban runoff mortality syndrome in coho salmon. However, the available data...
The current view is that environmental levels of nicotine and cotinine, commonly in the ng/L range, are safe for aquatic organisms. In this study, 7 days post-fertilization zebrafish embryos have been exposed for 24 h to a range of environmental concentrations of nicotine (2.0 ng/L-2.5 μg/L) and cotinine (50 pg/L-10 μg/L), as well as to a binary mi...
Glyphosate, a globally prevalent herbicide known for its selective inhibition of the shikimate pathway in plants, is now implicated in physiological effects on humans and animals, probably due to its impacts in their gut microbiomes which possess the shikimate pathway. In this study, we investigate the effects of environmentally relevant concentrat...
The acoustic startle response (ASR) is leaded by a sudden and intense acoustic stimulus. ASR has several forms of plasticity, including habituation and sensorimotor gating. Although ASR and its plasticity have been intensively studied in zebrafish (Danio rerio) larvae, information in adult zebrafish is still very scarce. In this manuscript we prese...
Parkinson’s disease (PD), the second most common neurodegenerative disorder, involves the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, resulting in motor and non‐motor symptoms. The neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) is widely used to develop chemical models of PD. This study evaluates...
The secondary neurotoxicity induced by severe organophosphorus (OP) poisoning, including paraoxon (POX), is associated with cognitive impairments in survivors, who, despite receiving appropriate emergency treatments, may still experience lasting neurological deficits. Thus, the present study provides a survival mouse model of acute and severe POX p...
The acoustic startle response (ASR) is an explosive motor response leaded by a sudden and intense acoustic stimulus. ASR has several clinically relevant forms of plasticity, including habituation and sensorimotor gating. Although ASR and its plasticity have been intensively studied in different animal models, including zebrafish (Danio rerio) larva...
Last year (2023) was the tenth anniversary of Toxics [...]
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, anxiety, hyperactivity, and interest restricted to specific subjects. In addition to the genetic factors, multiple environmental factors have been related to the development of ASD. Animal models can serve as crucial...
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, anxiety, hyperactivity, and restricted interest for specific subjects. In addition to the genetic factors, multiple environmental factors have been related to the development of ASD. Animal models can serve as crucia...
Citation: Tagkalidou, N.; Multisanti, C.R.; Bleda, M.J.; Bedrossiantz, J.; Prats, E.; Faggio, C.; Barata, C.; Raldúa, D. Analyzing the Effects of Age, Time of Day, and Experiment on the Basal Locomotor Activity and Light-Off Visual Motor Response Assays in Zebrafish Larvae. Toxics 2024, 12, 349. https://doi.org/ 10.3390/toxics12050349 Academic Edit...
Fungicides have been used in agriculture to control fungal infections in plants, such as stem rusts caused by pathogenic basidiomycetes, since the 1960s. French wine production receives a "cocktail" of more than ten types of broad-spectrum pesticides, not counting specific treatments to combat occasional infections. Among these vineyard-specific pr...
The presence of neuropathological effects proved to be, for many years, the main
endpoint for assessing the neurotoxicity of a chemical substance. However, in the
last 50 years, the effects of chemicals on the behavior of model species have
been actively investigated. Progressively, behavioral endpoints were incorporated
into neurotoxicological scr...
Zebrafish larvae are a model organism increasingly used in the study of the effect of neuroactive chemicals on vertebrate sleep/wake cycles. Sleep disturbances have a negative impact on mood, cognition and overall health. Here we present a protocol to assess over 24 h sleep/wake cycles in zebrafish larvae subjected to 12 h light/dark periods in 48-...
Glyphosate [N-(phosphonomethyl)glycine], the most widely used herbicide in the world, is a competitive inhibitor of 5-enolpyruvylsikimate-3-phosphate synthase (EPSPS), an enzyme of the shikimate pathway essential for the synthesis of aromatic amino acids in plants and some microorganisms, but not in animals. However, there are increasing evidences...
Fish have common neurotransmitter pathways with humans, exhibiting a significant degree of conservation and homology. Thus, exposure to fluoxetine makes fish potentially susceptible to biochemical and physiological changes, similarly to what is observed in humans. Over the years, several studies demonstrated the potential effects of fluoxetine on d...
The recent availability of commercial platforms for behavioral analysis in zebrafish larvae based on video-tracking technologies has exponentially increased the number of studies analyzing different behaviors in this model organism to assess neurotoxicity. Among the most commonly used assays in zebrafish larvae are basal locomotor activity (BLA) an...
In the mining basin of the Gafsa region in southwestern Tunisia, environmental exposure to randomly discharged phosphate-processing wastewaters (PPWW) presents a serious threat to health and the surrounding ecosystems. Thus, the contaminated areas are in continuous deterioration over time. There is a paucity of information on the deleterious effect...
Zebrafish larvae are a model organism increasingly used in the study of the effect of neuroactive chemicals on vertebrate sleep/wake cycles. Sleep disturbances have a negative impact on mood, cognition and overall health. Here we present a protocol to assess over 24 h sleep/wake cycles in zebrafish larvae subjected to 12 h light/dark periods in 48-...
This study aimed to investigate the influence of environmentally relevant fluoxetine concentrations on zebrafish development, assessing both embryotoxicity and behavior, antioxidant defense, gene expression and neurotransmitter levels at larval stage.
The increasing number of new psychoactive substances (NPS) entering the illicit drug market, especially synthetic cathinones, as well as the risk of cardiovascular complications, is intensifying the need to quickly assess their cardiotoxic potential. The present study aims to evaluate the cardiovascular toxicity and lethality induced by first-gener...
Carbaryl and fenitrothion are two insecticides sharing a common mode of action, the inhibition of the acetylcholinesterase (AChE) activity. Their use is now regulated or banned in different countries, and the environmental levels of both compounds in aquatic ecosystems have decreased to the range of pg/L to ng/L. As these concentrations are below t...
Carbaryl is a neurotoxic insecticide whose main mode of action (MoA) is the inhibition of the enzyme acetylcholinesterase (AChE). This chemical is currently highly regulated or banned in many countries, and the levels of carbary commonly found in non-directly exposed aquatic ecosystems are commonly at ng/L concentrations. The non-observed adverse e...
Carbaryl and fenitrothion are two insecticides sharing a common mode of action, the inhibition of the acetylcholinesterase (AChE) activity. Their use is now regulated or banned in different countries, and the environmental levels of both compounds in aquatic ecosystems have decreased to the range of pg/L to ng/L. As these concentrations are below t...
The number of people suffering from mental health problems is rising, with anxiety and depression now the most commonly diagnosed psychiatric conditions. Selective serotonin reuptake inhibitors (SSRIs) are one of the most prescribed pharmaceuticals to treat these conditions, which has led to their common detection in many aquatic ecosystems. As the...
Adrenoceptors are G protein-coupled receptors involved in a large variety of physiological processes, also under pathological conditions. This is due in large part to their ubiquitous expression in the body exerting numerous essential functions. Therefore, the possibility to control their activity with high spatial and temporal precision would cons...
Catecholamine‐triggered β‐adrenoceptor (β‐AR) signaling is essential for the correct functioning of the heart. Although both β1‐ and β2‐AR subtypes are expressed in cardiomyocytes, drugs selectively targeting β1‐AR have proven this receptor as the main target for the therapeutic effects of beta blockers in the heart. Here, we report a new strategy...
Hyperthermia is a common confounding factor for assessing the neurotoxic effects of methamphetamine (METH) in mammalian models. The development of new models of methamphetamine neurotoxicity using vertebrate poikilothermic animals should allow to overcome this problem. The aim of the present study was to develop a zebrafish model of neurotoxicity b...
Neuroactive chemicals are compounds that can modulate, at very low concentrations, the normal function of the central nervous systems of an organism through various primary modes of action (MoA) [...]
Summary Catecholamine‐triggered β‐adrenoceptor (β‐AR) signaling is essential for the correct functioning of the heart. Although both β1‐ and β2‐AR subtypes are expressed in cardiomyocytes, drugs selectively targeting β1‐AR have proven this receptor as the main target for the therapeutic effects of beta blockers in the heart. Here, we report a new s...
Catecholamine-triggered β-adrenoceptor (β-AR) signaling is essential for the correct functioning of the heart. Although both β 1 - and β 2 -AR subtypes are expressed in cardiomyocytes, drugs selectively targeting β 1 -AR have proven this receptor as the main target for the therapeutic effects of beta blockers in heart. Here, we report a new strateg...
Nowadays, there are countless articles about the harmful effects of paracetamol (PCM) in non-target organisms. Nonetheless, information regarding the toxicity of ciprofloxacin (CPX) and the CPX-PCM mixture is still limited. Herein, we aimed to evaluate the hepatotoxic and genotoxic effects that ciprofloxacin alone and in combination with paracetamo...
Hyperthermia is a common confounding factor for assessing the neurotoxic effects of methamphetamine (METH) in mammalian models. The development of new models of methamphetamine neurotoxicity using vertebrate poikilothermic animals should allow to overcome this problem. The aim of the present study was to develop a zebrafish model of neurotoxicity b...
Animal behaviour is closely related to individual fitness, which allows animals to choose suitable mates or avoid predation. The central nervous system regulates many aspects of animal behaviour responses. Therefore, behavioural responses can be especially sensitive to compounds with a neurodevelopmental or neurofunctional mode of action. Phototact...
Even though the toxic effects of paracetamol (PCM) and ciprofloxacin (CPX) have been deeply studied in the last decades, the impact of the PCM-CPX mixture may induce in aquatic organisms is poorly known. Thus, the objective of this work was to investigate the teratogenic effects and oxidative stress that PCM, CPX, and their mixture induce in Danio...
This study assessed the effects of the monoamine oxidase (MAO) inhibitor deprenyl in Daphnia magna locomotor activity. The mechanisms of action of deprenyl were also determined by studying the relationship between behaviour, MAO activity and neurotransmitter levels. Modulation of the D. magna monoamine system was accomplished by 24 h exposure to tw...
Fenitrothion is an organophosphorus insecticide usually found in aquatic ecosystems at concentrations in the range of low ng/L. In this manuscript we show that 24 h exposure to environmental concentrations of fenitrothion, from ng/L to low μg/L, altered basal locomotor activity, visual-motor response and acoustic/vibrational escape response of zebr...
This study examines the effects of acute pharmacological modulation of the serotonergic system over zebrafish larvae's cognitive, basic, and defense locomotor behaviors, using a medium to high throughput screening assay. Furthermore, the relationship between behavior, enzyme activity related to neurotransmitter metabolism, neurotransmitter levels,...
Zebrafish embryos and larvae are vertebrate models increasingly used in translational neuroscience research. Behavioral impairment induced by the exposure to neuroactive or neurotoxic compounds is commonly linked to changes in modulatory neurotransmitters in the brain. Although different analytical methods for determining monoaminergic neurochemica...
Glyphosate is the most widely used herbicide in the world. There is controversy regarding the potential neurotoxicity of glyphosate, since although some international agencies have classified this compound from non-neurotoxic (US EPA) to unlikely to be neurotoxic (EFSA), different studies have provided evidences of its potential neurotoxicity. In t...
Animal behaviour is closely related with individual fitness allowing animals to choose suitable mates or avoid predation. The central nervous system (CNS) regulates many aspects if not all of animal behaviour responses, therefore behavioural responses can be special sensitive to compounds with a neurodevelopmental or neurofunctional mode of action....
Glyphosate is the active ingredient of some of the most highly produced and used herbicides worldwide. The intensive applications of glyphosate-based herbicides and its half-life in water lead to its presence in many aquatic ecosystems. Whereas recent studies have reported neurotoxic effects of glyphosate including autism-related effects, most of t...
“The central nervous system regulates many aspects, if not all, of animal behavior responses. Phototactic behavior of preys such as Daphnia magna to fish predators is a central subject in ecology. Here we studied the neurological control of such behavior. Behavior results and HP LC/MS analysis indicated that agonists of the acetylcholine and GABA r...
“Environmental concentrations of glyphosate impair in adult zebrafish essential behaviors for survival in aquatic ecosystems. Results should be relevant not only for environmental risk assessment but also for human risk assessment of glyphosate.”
Metabolomics is currently an important field within bioanalytical science and NMR has become a key technique for drawing the full metabolic picture. However, the analysis of 1H NMR spectra of metabolomics samples is often very challenging, as resonances usually overlap in crowded regions, hindering the steps of metabolite profiling and resonance in...
Monoaminergic neurotransmitters are the main components that regulate of a lot of processes in the vertebrate brain. There is growing interest to monitor the changes produced in these neurochemicals due to the large number of exogenous agents, such as pharmaceuticals and drugs of abuse, targeting and affecting this system. Adult zebrafish (Danio re...
This study addresses short-term habituation of the escape response in the aquatic crustacean Daphnia magna evoked by sudden changes in light intensity, using a high-throughput system. Daphnia magna exhibits a marked phototactic behaviour and swim away from light to avoid predation by fish. Currently, there is no information available on the habitua...
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Predation is one of the main sources of mortality for fish larvae. During evolution, they have developed different anti-predator behaviours, as the vibrational-evoked startle response and its habituation, for promoting survival to predator's strikes. Whereas these two behaviours can be altered by the exposure to some neurotoxicants, it is currently...
Exposure to acrylamide may lead to different neurotoxic effects in humans and in experimental animals. To gain insights into this poorly understood type of neurotoxicological damage, we used a multi-omic approach to characterize the molecular changes occurring in the zebrafish brain exposed to acrylamide at metabolite, transcript and protein levels...
Two essential key events in acrylamide (ACR) acute neurotoxicity are the formation of adducts with nucleophilic sulfhydryl groups on cysteine residues of selected proteins in the synaptic terminals and the depletion of the glutathione (GSx) stores in neural tissue. The use of N-acetylcysteine (NAC) has been recently proposed as a potential antidote...
Organophosphorus compounds are acetylcholinesterase inhibitors used as pesticides and chemical warfare nerve agents. Acute organophosphorus poisoning (acute OPP) affects 3 million people, with 300,000 deaths annually worldwide. Severe acute OPP effects include overstimulation of cholinergic neurons, seizures, status epilepticus, and finally, brain...
Occupational, accidental, or suicidal exposure to acrylamide (ACR) may result in a neurotoxic syndrome. Development of animal models of acrylamide neurotoxicity is necessary for increasing our mechanistic understanding of this syndrome and developing more effective therapies. A new model for acute ACR neurotoxicity has been recently developed in ad...