Critical duration of exposure for developmental chlorpyrifos-induced neurobehavioral toxicity

Abstract

Developmental exposure of rats to the pesticide chlorpyrifos (CPF) causes persistent neurobehavioral impairment. In a parallel series of studies with zebrafish, we have also found persisting behavioral dysfunction after developmental CPF exposure. We have developed a battery of measures of zebrafish behavior, which are reliable and sensitive to toxicant-induced damage. This study determined the critical duration of developmental CPF exposure for causing persisting neurobehavioral effects. Tests of sensorimotor response (tap startle response and habituation), stress response (novel tank diving test) and learning (3-chamber tank spatial discrimination) were conducted with adult zebrafish after early developmental CPF exposure. The CPF exposure level was 100 ng/ml with durations of 0-1, 0-2, 0-3, 0-4 and 0-5 days after fertilization. Developmental CPF exposure had persisting behavioral effects in zebrafish tested as adults. In the tactile startle test, CPF exposed fish showed decreased habituation to startle and a trend toward increased overall startle response. In the novel tank exploration test, exposed fish showed decreased escape diving response and increased swimming activity. In the 3-chamber learning test, the 0-5 day CPF exposure group had a significantly lower learning rate. There was evidence for persisting declines in brain dopamine and norepinepherine levels after developmental CPF exposure. In all of the measures the clearest persistent effects were seen in fish exposed for the full duration of five days after fertilization. In a follow-up experiment there were some indications for persisting behavioral effects after exposure during only the later phase of this developmental window. This study demonstrated the selective long-term neurobehavioral alterations caused by exposure to CPF in zebrafish. The zebrafish model can facilitate the determination of the molecular mechanisms underlying long-term neurobehavioral impairment after developmental toxicant exposure.

Chlorpyrifos: pollution and remediation

“…Long lasting neurobehavioral deficits during early development, persistent hatching, larval morphological deformities, decrease in whole brain activity (Levin et al 2003(Levin et al , 2004Eddins et al 2009;Richendrfer et al 2012;Sledge et al 2011), reduced survival, adult length and body weight, and reproductive failure are the other primary effects likely to result from chronic chlorpyrifos exposures. Moreover, life cycle study has provided enough data to show that second generations are more sensitive than the first generation (Corbin et al 2009).…”

Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: II. A focus on growth impairment in fish

“…For example, certain toxicants are known to impair olfaction, interfering with the ability to recognize prey or causing aversion from particular food sources (LangerJaesrich et al, 2010;Tierney et al, 2010), while others can affect appetite (Baker et al, 1996;Gaworecki and Klaine, 2008;Mennigen et al, 2009). Yet other chemicals are reported to impair cognitive functions (Weis, 2009;Sledge et al, 2011). However, the most prominent and best-researched type of behavioral alterations that can be plausibly linked to reduction in food intake is impairment of locomotion, broadly understood as a failure to maintain normal performance levels of vital locomotory behavior components, such as activity patterns, speed of movements and orientation in space.…”

Zebrafish as potential model for developmental neurotoxicity testing

“…However, these end-organs consist of multiple macular compartments which are suggested to have multiple functions in detecting gravity and hearing in combination with the swim bladder, the Weberian ossicles and perilymphatic spaces (Popper and Fay, 1973). Due to the relative ease to investigate ototoxicity on lateral line hair cells, only a few studies have been carried out using hair cells of the (zebra)fish' inner ear (Giari et al, 2012;Yan et al, 1991).A behavioural screening method for detecting auditory response defects has been developed, since zebrafish react to a loud sound with a startle response, characterised by a brisk contraction of the body muscles, which is likely to be initiated by the Mautner system and other components of the brainstem neural network (Eddins et al, 2010;Sledge et al, 2011;Truong et al, 2012). However, the different components involved in hearing in teleost fish make it more difficult to translate the effects found to humans (Andersen et al, 2000;Bai et al, 2006;Bang et al, 2002;Popper and Fay, 1973).…”

“…Chlorpyrifos was found to have an adverse effect on spatial discrimination (Levin et al, 2003;Sledge et al, 2011). Neurodevelopmental exposure to bisphenol A, methylphenidate, selenomethionine, methylmercury or ethanol resulted in learning deficits in adult zebrafish (Carvan et al, 2004;Levin et al, 2011;Saili et al, 2012;Smith et al, 2010).…”