title: Freshwater Planarians as an Alternative Animal Model for Neurotoxicology.
abstract: Traditional toxicology testing has relied on low-throughput, expensive mammalian studies; however, timely testing of the large number of environmental toxicants requires new in vitro and in vivo platforms for inexpensive medium- to high-throughput screening. Herein, we describe the suitability of the asexual freshwater planarian Dugesia japonica as a new animal model for the study of developmental neurotoxicology. As these asexual animals reproduce by binary fission, followed by regeneration of missing body structures within approximately 1 week, development and regeneration occur through similar processes allowing us to induce neurodevelopment "at will" through amputation. This short time scale and the comparable sizes of full and regenerating animals enable parallel experiments in adults and developing worms to determine development-specific aspects of toxicity. Because the planarian brain, despite its simplicity, is structurally and molecularly similar to the mammalian brain, we are able to ascertain neurodevelopmental toxicity that is relevant to humans. As a proof of concept, we developed a 5-step semiautomatic screening platform to characterize the toxicity of 9 known neurotoxicants (consisting of common solvents, pesticides, and detergents) and a neutral agent, glucose, and quantified effects on viability, stimulated and unstimulated behavior, regeneration, and brain structure. Comparisons of our findings with other alternative toxicology animal models, such as zebrafish larvae and nematodes, demonstrated that planarians are comparably sensitive to the tested chemicals. In addition, we found that certain compounds induced adverse effects specifically in developing animals. We thus conclude that planarians offer new complementary opportunities for developmental neurotoxicology animal models.
authors.affiliation: *Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093;
authors.forename: Danielle
authors.initials: D
authors.lastname: Hagstrom
authors.affiliation: Physics Department, University of California, San Diego, La Jolla, California 92093; and.
authors.forename: Olivier
authors.initials: O
authors.lastname: Cochet-Escartin
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California 92093.
authors.forename: Siqi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: *Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093;
authors.forename: Cindy
authors.initials: C
authors.lastname: Khuu
authors.affiliation: *Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093; Physics Department, University of California, San Diego, La Jolla, California 92093; and emscollins@physics.ucsd.edu.
authors.forename: Eva-Maria S
authors.initials: EM
authors.lastname: Collins
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D004195:Disease Models, Animal; D005947:Glucose / Q000494:pharmacology; D007928:Lethal Dose 50; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D009498:Neurotoxins / Q000633:toxicity*; D010932:Planarians / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology*; D012038:Regeneration / Q000187:drug effects; D012100:Reproduction, Asexual; D013697:Thermosensing / Q000187:drug effects
chemical_list: D009498:Neurotoxins; D005947:Glucose
keywords: aquatic toxicology; behavior; developmental neurotoxicity; planarian; screening