Abstract
Developmental exposure to neurotoxic chemicals presents significant health concerns because of the vulnerability of the developing central nervous system (CNS) and the immature brain barrier. To date, a short list of chemicals including some metals have been identified as known developmental neurotoxicants; however, there are still numerous chemicals that remain to be evaluated for their potential developmental neurotoxicity (DNT). To facilitate evaluation of chemicals for DNT, the zebrafish vertebrate model system has emerged as a promising tool. The zebrafish possesses a number of strengths as a test species in DNT studies including an abundance of embryos developing ex utero presenting ease in chemical dosing and microscopic assessment at all early developmental stages. Additionally, rapid neurodevelopment via conserved molecular pathways supports the likelihood of recapitulating neurotoxic effects observed in other vertebrates. In this review, we describe the biological relevance of zebrafish as a complementary model for assessment of DNT. We then focus on a metalloid and two metals that are known developmental neurotoxicants (arsenic, methylmercury, and lead). We summarize studies in humans and traditional vertebrate models and then detail studies defining the toxicity of these substances using the zebrafish to support application of this model system in DNT studies.
Highlights
Developmental exposure to certain chemicals are suggested as possible causes of neurodevelopmental impairments including reduced intelligence quotient (IQ), autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) [1,2,3,4]
We summarize developmental neurotoxicity (DNT) studies of a known metalloid and two metal neurotoxicants in humans and traditional vertebrate models
When a study was conducted with 1-day old infants, researchers did find a negative relationship between the arsenic levels measured in cord blood and the neurodevelopmental status of newborns when evaluated by Brazelton Neonatal Behavioral Assessment Scale (III) [115]
Summary
Developmental exposure to certain chemicals are suggested as possible causes of neurodevelopmental impairments including reduced intelligence quotient (IQ), autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) [1,2,3,4]. Environmental contamination of arsenic, methylmercury, and lead is widespread, resulting in frequent human exposure raising public health concerns (reviewed in [16,17,18,19,20]) These toxicants are non-biometals that do not play a role in biological systems and have been associated with neurodevelopmental alterations in developing organisms [3,21,22,23]. The little progress in identifying the DNT of chemicals is in part due to the limitation of studies using conventional in vivo models (e.g., non-human primates and rodent models), of which experiments are laborious, time-consuming, and may not be cost-effective To this end, the zebrafish model system has emerged as a suitable complementary in vivo DNT test model.
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