title: A rapid throughput approach identifies cognitive deficits in adult zebrafish from developmental exposure to polybrominated flame retardants.
abstract: A substantial body of evidence has correlated the human body burdens of some polybrominated diphenyl ether (PBDE) flame retardants with cognitive and other behavioral deficits. Adult zebrafish exhibit testable learning and memory, making them an increasingly attractive model for neurotoxicology. Our goal was to develop a rapid throughput means of identifying the cognitive impact of developmental exposure to flame retardants in the zebrafish model. We exposed embryos from 6h post fertilization to 5 days post fertilization to either PBDE 47 (0.1μM), PBDE 99 (0.1μM) or PBDE 153 (0.1μM), vehicle (0.1% DMSO), or embryo medium (EM). The larvae were grown to adulthood and evaluated for the rate at which they learned an active-avoidance response in an automated shuttle box array. Zebrafish developmentally exposed to PBDE 47 learned the active avoidance paradigm significantly faster than the 0.1% DMSO control fish (P<0.0001), but exhibited significantly poorer performance when retested suggestive of impaired memory retention or altered neuromotor activity. Learning in the PBDE 153 group was not significantly different from the DMSO group. Developmental exposure to 0.1% DMSO impaired adult active avoidance learning relative to the sham group (n=39; P<0.0001). PBDE 99 prevented the DMSO effect, yielding a learning rate not significantly different from the sham group (n=36; P>0.9). Our results underscore the importance of vehicle choice in accurately assessing chemical effects on behavior. Active avoidance response in zebrafish is an effective model of learning that, combined with automated shuttle box testing, will provide a highly efficient platform for evaluating persistent neurotoxic hazard from many chemicals.
authors.affiliation: Department of Environmental and Molecular Toxicology, the Sinnhuber Aquatic Research Laboratory and the Environmental Health Sciences Center at Oregon State University, Corvallis, OR, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Truong
authors.affiliation: Department of Environmental and Molecular Toxicology, the Sinnhuber Aquatic Research Laboratory and the Environmental Health Sciences Center at Oregon State University, Corvallis, OR, United States.
authors.forename: David
authors.initials: D
authors.lastname: Mandrell
authors.affiliation: Davrick Solutions, LLC, Lake Oswego, OR, United States.
authors.forename: Rick
authors.initials: R
authors.lastname: Mandrell
authors.affiliation: Department of Environmental and Molecular Toxicology, the Sinnhuber Aquatic Research Laboratory and the Environmental Health Sciences Center at Oregon State University, Corvallis, OR, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Simonich
authors.affiliation: Department of Environmental and Molecular Toxicology, the Sinnhuber Aquatic Research Laboratory and the Environmental Health Sciences Center at Oregon State University, Corvallis, OR, United States. Electronic address: Robert.Tanguay@oregonstate.edu.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Tanguay
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced*; D003214:Conditioning, Classical / Q000187:drug effects; D004195:Disease Models, Animal; D004625:Embryo, Nonmammalian; D005411:Flame Retardants / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D011939:Mental Recall / Q000187:drug effects; D015027:Zebrafish
chemical_list: D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers
keywords: Flame retardants; Learning; Memory; Shuttle box; Zebrafish