Neurodevelopmental Toxicity After Early Postnatal Exposure To Lambda-cyhalothrin In Mice

BackgroundLambda-cyhalothrin (LCT) is a newer pyrethroid type II insecticide used all over the world, and has moderately neurotoxic to humans and animals, and also a mild stimulating effect on the eyes. It has neurotoxic in contact and stomach poisoning and certain repellent effect, but has no effect of absorption and fumigation. The neurotoxic of LCT is quick and persistence, and has resistance ability of rainwater, and has a broad spectrum of insecticide toxic. LCT will directly or indirectly into the water and soil regardless of the manner in which applied to crops and residues of which, cause it can enter the body through a variety of ways. Studies have shown that rats in the critical period of brain development before birth exposure to low doses of pyrethroids (pyrethrin propylene), can induce learning and memory dysfunction, leading to irreversible brain function in adults change effort. LCT is a kind of common pyrethroid insecticides widespread in China, the neurotoxicity caused by LCT cann't be ignored. General attention was given to acute pesticide poisoning, and also begun to concern about chronic toxic effects of low dose exposure, However, the awareness and concern of the long-term neurodevelopmental toxicity of chronic pesticide exposure has not yet been produced.ObjectiveTo explore the sensitive neurobehavior indexs of exposured to LCT in mice by a series methods of behavior, the results can be referenced in neural developmental toxicity in human. The oxidative stress and synapsins was observed to investigate neural developmental toxicity mechanism of LCT. MethodsTechnical grade LCT was dissolved in DMSO at concentrations of 0, 0.1, 1, 10mg/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 5 groups, experimental group received LCT, one control group was treated with saline solution on a similar schedule and the other was DMSO. On postnatal 5(PND5), 7, 9, 11and 13 , all pups were intragastric administration after weigt (20ul/g). Mice were sacrificed at 24 h after last administration (PND 13), Quickly isolated cortex, hippocampus, striatum of the right hemisphere,and used for synapsins tested by Western blot, Cerebellum for the detection of oxidative stress indicators; left brain used for immunohistochemical examination.ResultsEarly exposure to LCT body can affect offspring development of motor coordination, in the forelimb suspension, rooting reflex experiments, with the dose increased, standard extended (r = 0.97, P <0.05). No abnormalities in mice during the performance, body and brain weight,indicators of neurobehavioral development in each group were not significantly different. GSH in the cerebellum reduced and MDA increased in the 10 mg/kg group of mice (P <0.05). GFAP in the LCT exposed mouse cortex and hippocampus was increased in a dose-depended manner (male:r hippocampus =0.986, r cortex =0.945, female: r hippocampus =0.993, r cortex =0.969,All P <0.05), while Tuj protein expression did not change significantly in the various brain regions of ICR mice. Gap43 protein expression was dose-dependently increased in the LCT exposed mouse hippocampus and in female ICR mouse cortex (male:r hippocampus =0.882,female:r hippocampus = 0.997, r cortex =0.99, All P<0.05). Presynaptic protein synapsinâ… did not change significantly in various brain regions. However, postsynaptic density protein 95 (PSD95) expression decreased in 10mg/kg groups of the hippocampus, striatum, cortex of male offspring and female LCT groups in hippocampus and 1.0,10.0 mg/kg group of striatum (P <0.05). PSD95 expression was dose-dependent decrease in hippocampus of male rats, female pups striatum and cortex by spearman correlation analysis (male:r hippocampus =-0.991, female:r striatum =-0.996,r cortex =-0.995, All P<0.05).ConclusionsEarly postnatal exposure to LCT affects the sensitivity of offspring development and motor coordination, there is oxidative stress injury of the cerebellum, and cortex, hippocampus, striatum synaptic protein expression to a certain extent , These effects may ultimately affect the construction of synaptic connections.