This proposal will be testing the hypothesis that exposure of the very early embryo to compounds that can impact upon neuronal signaling will result in adults with learning and or behavioral problems. Its three specific aims are: 1) to examine how ectopic signaling through the acetylcholine pathway results in changes that eventually influence adult learning/behavior;2) to test whether signaling interference in the glycine and GABA pathways impact upon adult learning/behavior and to examine the molecular/developmental changes imposed and 3) to evaluate whole embryo effects of environmental chemicals that might affect neuronal signaling. Its potential value to human health is related to the large number of chemicals that have been and are being introduced into our environment without an adequate amount of pediatric or embryonic neurological examination. We have previously found that very early exposure of the zebrafish embryo to chlorpyrifos results in adults with learning deficiencies. In this proposal we plan to examine the early events affected by this challenge and to challenge other neurotransmitter pathways to test the generality of the hypothesis. The technologies used will include behavioral analyses, the creation and use of a number of fluorescent transgenic reporter lines to fish, microarray analysis, and HPLC analysis of neurotransmitter levels.
This research is focused upon examining whether environmental compounds that the developing nervous system comes in contact with can affect learning and, or, behavior in adult life. It is focused upon developing and using a model vertebrate system to both address this question and possible mechanisms that would be responsible for later learning and, or, behavioral effects upon the adult. Compounds that could affect this result include pesticides and pharmaceuticals that the fetus or young children might contact.
| Yen, Jerry; Donerly, Sue; Levin, Edward D et al. (2011) Differential acetylcholinesterase inhibition of chlorpyrifos, diazinon and parathion in larval zebrafish. Neurotoxicol Teratol 33:735-41 |
| Linney, Elwood; Donerly, Susan; Mackey, Laura et al. (2011) The negative side of retinoic acid receptors. Neurotoxicol Teratol 33:631-40 |
| Sledge, Damiyon; Yen, Jerry; Morton, Terrell et al. (2011) Critical duration of exposure for developmental chlorpyrifos-induced neurobehavioral toxicity. Neurotoxicol Teratol 33:742-51 |
| Levin, Edward D; Sledge, Damiyon; Roach, Stephanie et al. (2011) Persistent behavioral impairment caused by embryonic methylphenidate exposure in zebrafish. Neurotoxicol Teratol 33:668-73 |
