Planarians as a model to study neurotoxic agents

The developing brain is more vulnerable to chemicals than the adult brain, but environmental chemicals have only been sparingly tested for developmental neurotoxicity (DNT). This data sparsity arises from the extreme cost and duration of mammalian toxicity testing required for regulatory decision making. To close this knowledge gap, alternative non-animal test methods are being developed for rapid and cost-effective screening. While all models have limitations, integrated testing strategies that incorporate data from multiple test methods, spanning computational, in vitro, and in vivo approaches, promise to better predict human toxicity. In vivo models using invertebrates allow for rapid systems-level toxicity testing to complement human cell culture models that lack this capacity. Behavior is used as a functional readout of nervous system operation, while morphological and biochemical assays can assess damage to physiological and cellular processes. Freshwater planarians have emerged as a new invertebrate model for systems-level neurotoxicity and DNT testing. Planarians regenerate their brain following head amputation or asexual reproduction. For asexual planarians, neuroregeneration is the sole form of neurodevelopment. Because adult and regenerating planarians are of similar size, effects on adult/intact and regenerating/developing planarians can be tested in parallel to distinguish neurotoxicity from DNT in a single experiment. This unique advantage and the planarian's rich, quantifiable behavioral repertoire have driven its recent gain in popularity. Here, we briefly introduce planarian neurobiology and behavior, and review how testing with this exciting non-animal organismal model can fill existing gaps in neurotoxicity and DNT studies—with a special focus on organophosphorus agents.