| Arsenic is a very important element of the earth crust, which exist in the rock in the form of inorganic compound, gradually come into aquatic environment and soil environment by wind erosion and water corrosion, and little disperse in the air. Arsenic exposure of human is due to drink the groundwater with rich arsenite. At present, the worldwide population drinking the water with rich arsenite is 200 million, while the population exposed to high amounts of arsenic in Mainland of China is estimated to be more than three million. Arsenic exposure during a long term may induce cancers, non-carcinogenic effects and many other multisystem diseases and affect skin, heart, lung, bladder, pancreatic islet and many other organs.Except for the toxic effects above, it's reported that arsenic may influence the ability of memory in recent studies. A large number of epidemiological studies suggested that arsenic had the potential to modify brain physiology and lead to mental retardation and developmental disabilities such as physical, cognitive, psychological, sense and speech impairment. Experiments in vitro also showed that arsenic might affect the ion channels and interfere some important functions of cell such as LTP. Because the epidemiological studies can't determine the casual relationship and the results of experiments in vitro is difficult to be extrapolated to the human body, the studies of arsenic neurotoxicity in animal level play an important role in approaching the pathogenesis of arsenic poisoning and prevent the occurrence of arsenic poisoning.The memory of human can be theoretically divided into different memory models in which episodic memory is the most basic and the simplest model. The spatial memory of rodents is generally used to imitate the episodic memory of human. The neuron of hippocampus plays an important role in the formation of episodic memory, while the synaptic plasticity is the foundation of this role. It has been confirmed that there is close relationship between the plasticity of mossy fiber and the ability of spatial memory of rats. The aim of this study is to establish the animal model of chronic arsenic poisoning, determine the ability of spatial memory by Morris water maze and Y maze, investigate the underlying mechanism and construct the foundation for clarifying the neurotoxicity of arsenic in further study.Purpose:Establish the animal model of chronic arsenic poisoning by administrating arsenite through drinking water. Examine whether arsenite exposure affect the spatial memory of rats and investigate the injury degree of hippocampal neuron by arsenic and the plasticity of mossy fiber.Methods:1.Sixty weaning SD male rats were randomly divided into three group:control group, low-dose group(10mg/kg), high-dose group(15 mg/kg). The animal model of chronic arsenic poisoning was established by administrating arsenite through drinking water for 3 months. The concentration of arsenic in blood and brain was determined by atomic fluorescence absorption spectrometer.2.The ability of spatial memory was determined by maze experiments: the spatial reference memory of SD rats was examined by Morris water maze and the spatial working memory was examined by Y maze.3.The ultra-structural changes of myelin sheath of hippocampal neurons were observed by an electron microscope. The situation of mossy fibers was showed by the Timm's staining.Results:1.The animal model of chronic arsenic poisoning was successfully established by administrating arsenite through drinking water. The content of arsenic in blood and brain both was increasing in a dose-response manner(p<0.05).2.Hidden platform test suggested the latency to reach the platform of rats from high-dose group was significantly longer than rats from control group (p<0.05); the probe test showed the stay time of target quadrant of rats from high-dose group was significantly shorter than rats from control group (p<0.05); the transferred platform test suggested there is no significant difference in latency of rats from three groups (p>0.05); Y maze suggested the correct rate of rats from control group is significantly better than those from high-dose group(p<0.05).3.The electron microscope showed the myelin sheath was loosed and mitochondrial in axon was injured. Timm's staining showed that comparing with the control group, it's significantly reducing that the area of mossy fiber terminal in stratum oriens of CA3 area in hippocampus of rats from high-dose group(p<0.05).Conclusions:In this study, the animal model of chronic arsenic poisoning was successfully established by administrating arsenite through drinking water. The results showed: 1.The arsenite exposure severely inhibited the weight gain of rats and caused the arsenic accumulation in blood and brain. 2. The arsenite exposure caused the dysfunction of the spatial reference memory, however, the strategies to locate the platform wasn't affected. The spatial working memory was also injured. 3. The ultra-structure of myelin sheath of hippocampal neurons was changed and the plasticity of mossy fibers was injured. The results suggested arsenite exposure may influence the neogenesis of neuron in hippocampal dentate gyrus, thereby injury the plasticity of mossy fibers and cause dysfunction of spatial memory eventually, which construct the foundation for clarifying the neurotoxicity of arsenic in further study. |
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