Browsing by Author "Levin, Edward Daniel"
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Item Open Access The Neurobehavioral and Developmental Effects of Flame Retardants on Zebrafish(2017-05-08) Drastal, Meghan; Glazer, Dr LilahFlame retardants are added to a large range of consumer products—including textiles, furniture, electronics and building materials—for the purpose of preventing or slowing the the spreading of fires. Human exposure to flame retardants has been shown to occur through both ingestion of indoor air and absorption of dust particles through the skin. In recent years, concern pertaining to the health and environmental implications of certain categories of flame retardants has led to the phasing out of these chemicals and replacement with alternatives, such as organophosphate (OP) flame retardants. Thus, the present study investigates whether developmental exposure to low levels of these chemicals will result in measurable behavioral effects at early or later life stages. Zebrafish eggs are exposed to flame retardant chemicals, an OP pesticide of known neurotoxicity, or a vehicle control consisting of 0.01% solution of dimethyl sulfide oxide (DMSO) for 5 days post-fertilization. After exposure, larvae swim behavior is tested. The 6-day old larvae are then transferred to aquarium water and allowed to develop normally. The adult zebrafish are tested on a battery of assessments examining anxiety-related behavior, sensorimotor integration, predatory escape, sociability, and cognitive ability. The ultimate aim is to evaluate the safety profiles of these compounds and determine whether zebrafish high throughput behavioral assays are an effective model for characterizing neurotoxicity.Item Open Access The Role of Dopaminergic Systems in the Neurobehavioral Teratology of Organophosphates in Zebrafish(2016) Oliveri, AnthonyBackground: Organophosphate (OP) pesticides are well-known developmental neurotoxicants that have been linked to abnormal cognitive and behavioral endpoints through both epidemiological studies and animal models of behavioral teratology, and are implicated in the dysfunction of multiple neurotransmitters, including dopamine. Chemical similarities between OP pesticides and organophosphate flame retardants (OPFRs), a class of compounds growing in use and environmental relevance, have produced concern regarding whether developmental exposures to OPFRs and OP pesticides may share behavioral outcomes, impacts on dopaminergic systems, or both. Methods: Using the zebrafish animal model, we exposed developing fish to two OPFRs, TDCIPP and TPHP, as well as the OP pesticide chlorpyrifos, during the first 5 days following fertilization. From there, the exposed fish were assayed for behavioral abnormalities and effects on monoamine neurochemistry as both larvae and adults. An experiment conducted in parallel examined how antagonism of the dopamine system during an identical window of development could alter later life behavior in the same assays. Finally, we investigated the interaction between developmental exposure to an OPFR and acute dopamine antagonism in larval behavior. Results: Developmental exposure to all three OP compounds altered zebrafish behavior, with effects persisting into adulthood. Additionally, exposure to an OPFR decreased the behavioral response to acute D2 receptor antagonism in larvae. However, the pattern of behavioral effects diverged substantially from those seen following developmental dopamine antagonism, and the investigations into dopamine neurochemistry were too variable to be conclusive. Thus, although the results support the hypothesis that OPFRs, as with OP pesticides such as chlorpyrifos, may present a risk to normal behavioral development, we were unable to directly link these effects to any dopaminergic dysfunction.