Developmental Deltamethrin Exposure Causes Persistent Changes in Dopaminergic Gene Expression, Neurochemistry, and Locomotor Activity in Zebrafish

• Published in: Toxicological sciences Vol. 146; no. 2; pp. 235 - 243
• Main Authors: Kung, Tiffany S, Richardson, Jason R, Cooper, Keith R, White, Lori A
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.08.2015
• Subjects: Alteration in Zebrafish Dopamine Function by Deltamethrin; Animals; Female; Gene Expression Regulation, Developmental - drug effects; In Vitro Techniques; Insecticides - toxicity; Methylphenidate - pharmacology; Nitriles - toxicity; Pregnancy; Prenatal Exposure Delayed Effects; Pyrethrins - toxicity; Receptors, Dopamine D1 - genetics; Receptors, Dopamine D2 - genetics; Swimming; Zebrafish - embryology; developmental exposure; locomotor activity; zebrafish; dopamine; pyrethroid
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/kfv087

Pyrethroids are commonly used insecticides that are considered to pose little risk to human health. However, there is an increasing concern that children are more susceptible to the adverse effects of pesticides. We used the zebrafish model to test the hypothesis that developmental exposure to low doses of the pyrethroid deltamethrin results in persistent alterations in dopaminergic gene expression, neurochemistry, and locomotor activity. Zebrafish embryos were treated with deltamethrin (0.25-0.50 μg/l), at concentrations below the LOAEL, during the embryonic period [3-72 h postfertilization (hpf)], after which transferred to fresh water until the larval stage (2-weeks postfertilization). Deltamethrin exposure resulted in decreased transcript levels of the D1 dopamine (DA) receptor (drd1) and increased levels of tyrosine hydroxylase at 72 hpf. The reduction in drd1 transcripts persisted to the larval stage and was associated with decreased D2 dopamine receptor transcripts. Larval fish, exposed developmentally to deltamethrin, had increased levels of homovanillic acid, a DA metabolite. Since the DA system is involved in locomotor activity, we measured the swim activity of larval fish following a transition to darkness. Developmental exposure to deltamethrin significantly increased larval swim activity which was attenuated by concomitant knockdown of the DA transporter. Acute exposure to methylphenidate, a DA transporter inhibitor, increased swim activity in control larva, while reducing swim activity in larva developmentally exposed to deltamethrin. Developmental exposure to deltamethrin causes locomotor deficits in larval zebrafish, which is likely mediated by dopaminergic dysfunction. This highlights the need to understand the persistent effects of low-dose neurotoxicant exposure during development.