Effects Of Carbon Tetrachloride Long-time Exposureon Dendritic Spine And Synapse Of Hippocampus In Mice

Exposure to carbon tetrachloride (carbon tetrachloride, CCl4) causes damage of liver, kidney and thenervous system depression. It is a serious harm to human health. Currently the studies on CCl4toxicitymainly focused on the toxicity of liver and kidney and its related mechanism, however, research on thedamage of CCl4to the nervous system is not deep enough. Especially the in vivo observation on the effectsof long-term exposure to CCl4on neuronal morphology and function was rarely reported. Hippocampus isclosely related to learning and memory, and it is an ideal target organ for the neurotoxicological studies.The dendrite spines and synapses are the main functional structure of neurons. They are sensitive totoxicants and other neurotoxin. So the pathology change of the structure and function in the dendrite spineand synapses are often as the causes of poison damage and dysfunction of certain diseases of nervoussystem.ObjectiveThe objective of this study is to establish a model of long-term exposure to CCl4to simulatelong-term exposure to CCl4. The effects of long-term exposure to CCl4in mice on dendritic spines andsynapses of hippocampal pyramidal cell were observed.MethodsThis study established a model of long-term exposure to CCl4to simulate long-term exposure to CCl4.Morris water maze was used to observe the effects of long-term exposure to CCl4on the ability of learningand memory in mice. By use of DiI-diotistic labeled neurons method, immunofluorescence techniques andtransmission electron microscopy, the changes of long-term exposure to CCl4in mice on dendritic spinesand synapses of hippocampal pyramidal cell were observed.Results(1) Morris water maze was used to observe the effects of long-term exposure to CCl4on the abilityof learning and memory in mice. In acquired training, although the difference of the mean latency betweenCCl4high dose group and CCl4low dose group in mice did not reach significance level (P>0.05), the latency in the control group was much lower that that of the two CCl4group. The difference among thecontrol group and the CCl4groups was significant (P<0.05). It was concluded that CCl4there was asignificant difference in the among the CCl4group and control group. The ability of learning and memoryin the CCl4groups was less than the control group, and the difference was significant.(2) The DiI-diotistic labeled neurons method was used to label the hippocampal pyramidal cells foreach experimental group. The confocal microscopy was use to observe the pathological changes ofdendritic spines. The results indicated that long-term exposure to CCl4could induce the density ofhippocampal pyramidal cells reduction (reducing in the number), increasing the length, and hasdose-relation and long-time potentiation.(3) By use of immunofluorescence techniques, synaptophysin was used to label the mice in thecontrol group and the drug group (low-dose and high-dose group). The results showed that the number ofpositive synaptophysin fluorescence particles in hippocampal synaptic in drug group was reduced as thedose of long-term exposure to CCl4was increased, suggesting that long-term exposure to CCl4causedsynaptic reduction and this reduction was dose-related.(4) The ultrastructure of synapses in control groups and drug group was observed by use oftransmission electron microscopy. Results showed that the synaptic structure had a certain change.Compared with the control group, synaptic vesicles were decreased in both groups, and the synaptic gapbecame blurred.ConclusionIn short, exposure to CCl4can reduce the ability of learning and memory in mice, resulting tomorphology of dendritic spines and synapses in hippocampal pyramidal cells in mice changes and missingof the number, and the impact on the nervous system were with dose-related and long-term potentiation.This study would provide the basic evidence for development of chronic drug or health food tointerfere the toxic effects of carbon tetrachloride.