Premium
Comparative Analysis of Organophosphate Developmental Neurotoxicity in a Freshwater Planarian
Author(s) -
Hagstrom Danielle,
Zhang Siqi,
Hirokawa Hideto,
Taylor Palmer,
Collins EvaMaria S.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1191.5
Subject(s) - planarian , acetylcholinesterase , neurotoxicity , planaria , diazinon , biology , zebrafish , chlorpyrifos , organophosphate , aché , toxicology , pharmacology , toxicity , regeneration (biology) , neuroscience , microbiology and biotechnology , pesticide , medicine , biochemistry , ecology , enzyme , gene
Organophosphates (OPs) are among the most commonly used pesticides in the U.S. and act by irreversibly inhibiting acetylcholinesterase (AChE), leading to cholinergic overstimulation due to increased synaptic levels of acetylcholine, paralysis and death. Their environmental abundance, although below acutely toxic levels to humans, has been suggested to be at least partially responsible for the observed increase in childhood neurodevelopmental disorders. However, it is unknown through which mechanisms chronic, low‐dose prenatal and infant OP exposure causes neurotoxicity in the developing brain. In this study, we analyzed the toxicological profiles of five common OPs (chlorpyrifos, dichlorvos, diazinon, malathion and parathion) using a multi‐endpoint planarian screening platform. The freshwater planarian, Dugesia japonica , is an excellent in vivo model for developmental neurotoxicology studies because its remarkable regenerative capabilities allows development to be induced at will by amputation. Moreover, because of their short development time (12 days) and similar size, regenerating and adult animals can be tested simultaneously using the same assays to identify development‐specific toxicity. Importantly, despite its simplicity, features of the planarian brain are conserved in the mammalian brain on the molecular and structural levels making mechanistic analysis of neurotoxicity in this animal directly relevant to human health. With this platform, we characterized effects on lethality, regeneration and a range of stimulated and unstimulated behaviors. We found that the different OPs varied widely in toxic dose, affected endpoints and developmental sensitivity. Lastly, through biochemical analysis of AChE activity in OP‐treated animals, we found that, depending on the OP, prolonged inhibition of AChE was not necessary for or necessarily indicative of toxic effects. This indicates that toxicity may be induced by alternative mechanisms, necessitating further in depth mechanistic studies. Support or Funding Information DH supported by the NIH Cellular and Molecular Genetics Training Grant. EMSC supported by the Hellman foundation, the Burroughs Wellcome Fund CASI award and the Alfred P. Sloan Fellowship