Neurodevelopmental Toxicity After Early Postnatal Exposure To Fenvalerate In Mice

BackgroundFenvalerate belongs to type II Pyrethroids and is highly neurotoxic. Pyrethroid insecticides are widely used in the world. humans are exposed to Pyrethroids from various environmental sources. Extensive studies on animals revealed that Pyrethroids are particularly toxic to neurons, acting directly on the axon by interference with the sodium channel gating mechanism that underlies the generation and conduction of nerve impulses. the potential for developmental toxicity of Pyrethroids is not well understood, little is known about the neurotoxicity of chronic exposure to moderate levels of Fen, In relation to the early development of the young mice CNS and the exposure of Fenvalerate.ObjectiveTo explore the sensitive neurobehavior indexs of exposured to FEN in mice by a series methods of behavior, the results can be referenced in neural developmental toxicity in human. The protein expression of GAP-43 was observed by Western blot, to investigate neural developmental toxicity mechanism of FEN.MethodsTechnical grade Fenvalerate was dissolved in DMSO at concentrations of 0, 0.05,0.5, 5mg/kg. Forty sexually naive female mice were mated with males previously tested as fertile (2 females and 1 male in each cage). The presence of sperm in a vaginal smear test was considered a positive mating. These females were then removed from the male cage and housed individually. After delivery, all litters were examined externally for the presence of gross abnormalities, sexed and weighed; ten pups (5 males and 5 females) were assigned to each dam. pups of each dam were divided into 5groups,experimental group received Fen, one control group was treated with saline solution on a similar schedule and the other was DMSO. On postnatal 3(PND3), 5, 7, 9, 11and 13 , all pups were peritoneal injection after weigt (2ul/g). After 6 times injection, the mice keep living till adult, observe physiological growth, sensory movement and loctomotion and harmony ability of little mouse by a series methods of developmental neurobehavior include open field, balance beam test and Morris water maze. The protein expression of GAP-43 was observed by Western blotting.ResultsThere was a trend towards decreased vaginal opening time and discrimination ratio in novel-object recognition task in the high dose group. FEN-exposure induced reversible effects on sensorimotor activity which were measured by negative geotaxis test (PND 7) and horizontal bar task (PND 70). FEN-exposure did not alter mice behavior in open-field, but FEN-exposure (dose group 5.0 mg.kg-1) decreased number of platform-site crossovers in probe trial of MWM test compared to DMSO control.ConclusionsFEN-exposure induced reversible effects on sensorimotor activity which were measured by negative geotaxis test and horizontal bar task , but FEN-exposure (5.0 mg.kg-1) decreased number of platform-site crossovers in probe trial of MWM test compared to DMSO control. The results suggest that early postnatal exposure to FEN affects spatial memory in adult mice.