| Background Dieldrin is an Organochlorine insecticide which belongs to the persistentorganic pollutants, it can produce the damages to the central nervous system. Dieldrinwas once widely used in China. Although it has been disabled for many years, there arestill residues of dieldrin in the environment, food and milk because of its high toxicityand bioaccumulation. Numerous studies have shown that dieldrin has reproductivetoxicity and endocrine disruption functions. However, the mechanism ofneurodevelopmental toxic effects caused by short time exposure to low-dose dieldrinduring the early period of life is still little known about.Objective Expose postnatal early mice to different concentrations of low doses ofdieldrin by intraperitoneal injection during the critical period of brain development, toobserve the general developmental status of mice, the appearance of hippocampalneurons and the number of neurons in different regions of hippocampus. Study thelevels of hippocampal synaptic protein in mouse lactation, adolescence and adulthoodby Western Blotting. Then to further explore the mechanism of neurodevelopmentaltoxic effects of dieldrin.Methods Mating the ICR mice to plan pregnancy. Adjust the mice to10in everylitter after birth. Each litter was randomly divided into5groups, respectively, the highdose groups (20.0μg/kg), the medium dose groups (2.0μg/kg), the low dose groups(0.2μg/kg) dieldrin treated groups and dimethyl sulfoxide (DMSO) solvent controlgroup and normal saline (NS) group. Exposed dieldrin (2μl/10g) from the third day afterbirth (PND3) by intraperitoneal injection, and carried out the injections every other dayfor six consecutive times. During the general growth and development phase, indicated the possible signs including the weight of body, fluff and the time of eyes opening andso on. From on the day of PND92, carried out programmed Morris water mazeexperiment for a total of6days, to test the ability of learning and memory of mice.Made anesthesia and perfusion, then killed those mice and separated the brain tissue inlactation (PND14), adolescent (PND36) and adulthood (PND98) respectively. The lefthemisphere was fixed by paraformaldehyde and dried by gradient sucrose dehydration,for frozen section to save in-40℃. Further for Thionin staining positioning, neuroncounting and immunohistochemistry fluorescence. The right hemisphere rapidseparation of the hippocampus was stored at-80℃. Study the levels of Synapsin I ofpresynaptic membrane protein and PSD95of postsynaptic membrane protein bywestern blotting.Results There was no inflammatory response in injection sites of mice. Those datasof development like body fluff, activity, general growth were normal and had nodifferences during the experiment of each group, and so did the weight gain. Whilecounting the numbers of neurons in different partition of hippocampus, we found thatthe relative value number of high-dose group in female mice CA1and CA3partition ofhippocampus reduced significantly from adolescence, and continued to adulthood, butthe relative value number of high-dose group in male mice CA1and CA3partition ofhippocampus reduced only till adulthood (P<0.05). During the Morris water mazeexperiment we found that staging incubation period of all dose groups of adulthood wassignificantly shorter, and the stage incubation period of the fifth and the sixth day inadult high dose group prolonged a lot. Among the exploring experiment after24hours,it shown that the times through the location of original target platform reduced both inmale and female mice (compared with the solvent control group, P<0.05).By detectingthe expression of Synaptic marker proteins, we found that the postnatal exposure todieldrin can significantly decrease the level of presynaptic protein (Synapsin I) of thefemale hippocampus in high-dose group during lactation, it reduced till adolescence, even to adulthood. The level of postsynaptic density protein95(PSD95) had a dosedependent decrease (rPND36=-0.822, P<0.05), and continued to adulthood (rPND98=-0.743, P<0.05). But the levels of hippocampus presynaptic protein (synapsin I) had noobvious change in male mice of each group. However, the levels of PSD95expressionof the male hippocampus in high-dose group all significantly decreased during variousstages of development (lactation, adolescence and adulthood).Conclusions Early postnatal exposure to dieldrin will damage the late stage abilityof learning and memory of mice, influence the appearance and structure of neurons inCA3partition of hippocampus and reduce the number of neurons in hippocampal CA1and CA3partitions. The main reason of decline in learning and memory may be thatdieldrin reduced the expression of hippocampal synaptic protein, and then effected theestablishment of synaptic connections and synaptic plasticity. This suggests that lowdoses of dieldrin exposure may persistently damage hippocampal synaptic connectionsand thus affect the function learning and memory... |
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