Neurodevelopmental Toxicity After Early Postnatal Exposure To Dieldrin In Mice

BackgroundDieldrin belongs to organochlorines and was developed in the middle of the last century. Dieldrin was first synthesized in laboratory[1] in 1946, and was widly used as an insecticide in 1950s. Dieldrin had neurological toxicity. Richardson JR,etc[2]studies show that maternal oral exposure during pregnancy with low doses of dieldrin (3 mg·kg-1, oral LD50 is 65 mg·kg-1),can harm offspring nigrostriatal dopaminergic system and increase the susceptibility of other nerve agents (eg,MPTP). Hatcher JM et al[3]studies show that PND63 male mice treated with low doses of dieldrin (3 mg·kg-1, 1 mg·kg-1, 0.3 mg·kg-1) can harm the nigrostriatal dopaminergic system. The potential for developmental toxicity of organochlorines is not well understood, little is known about the neurotoxicity of early postnatal exposure to moderate levels of dieldrin.ObjectiveTo observe the effects of early postnatal exposure to dieldrin on neurobehavior and spatial learning and memory ability in adolescence and adult mice. The results can be referenced in neural developmental toxicity in human. The protein expression of GFAP was observed by Western blot, to investigate neural developmental toxicity mechanism of dieldrin.MethodsICR mice pups randomly divided into 5 groups were received intraperitoneal injections (i.p.) of different doses of dieldrin (20, 2, 0.2μg·kg-1 ), DMSO solution and normal saline respectively every other day during postnatal days (PND) 3-13. The general physiological condition and neural development of mice during experiment were evaluated, and a battery of tasks i.e. hole-board test, spontaneous locomotor apparatus, beam walking, open field, Morris water maze (MWM), was used to assess the spontaneous motor activity, sensorimotor activity, anxiety and spatial learning and memory ability in different time.Mice were sacrificed in PND36 and PND98, substantia nigra striatum was separated from brain. The protein expression of GFAP was observed by Western blotting.ResultsThere were trends toward decreased vaginal opening time and delayed testicular descent time. Dieldrin-exposure induced reversible effects on sensorimotor activity which were measured by negative geotaxis test (PND 1) and horizontal bar task. Dieldrin-exposure did not alter mice behavior in open-field, but dieldrin-exposure decreased number of platform-site crossovers in probe trial of MWM test compared to DMSO control. Dieldrin-exposure induced the increasing GFAP's expression.ConclusionsDieldrin-exposure induced reversible effects on sensorimotor activity which were measured by negative geotaxis test and horizontal bar task , but dieldrin-exposure decreased number of platform-site crossovers in probe trial of MWM test compared to DMSO control. The results suggest that early postnatal exposure to dieldrin affects spatial memory in adult mice. Limited times of early postnatal exposure to dieldrin increase the expression of GFAP in the nigrostriatal systerm.