| Objective: By exposing adult male mouse to chronic adverse stress and applying enriched environment intervention, to assess the short-term and long-term effects on mice cognitive function and the change of hippocampus pathobiology, and approach the possible mechanism, hoping to find out the possible etiological factor of AD and the new prevention measures.Method: Adult male Kunming mouse at the age of eight weeks are brought to suit environment one week, then randomizedly divided into chronic stress group(S group), stress and enriched environment group(SE group) and control group. Then according to varied time, divide the above every group mouse into adult group and aged group when the sample are chosen. Group S and group SE are exposed to restrained stress for six weeks and six hours one day, by difference, group S are reared in common environment and group SE are reared in enriched environment. Six weeks later, assess the ability of learning and memory of adult mouse by water maze; after that, take their brain tissue, synaptophysin histochemical staining with method SP, observe the changes of synaptophysin of hippocampus CA1, CA2 and dentate gyrus, and then analyze synaptophysin positive cells by computer and acquire immunes histochemistry positive cell score(IHS); meanwhile observe the changes of Nissl's body within hippocampus neuron endochylema, stained by thionine. The aged group mouse are reared under common environment for ten weeks until old stage (totally 25 weeks old) and handled with adult mouse. At last display all the experimental data with X±S and analyze the data with statistic software SPSS10.0.Result: 1. Group adult mouse: the learning and memory records for mouse group S are 93.00±35.06 Sec, 75.25±34.35 Sec, which are longer than mouse SE and control group (records for SE group are 20.44±3.88 Sec, 22.22±7.82 Sec, and control group are 19.00±2.22 Sec, 20.00±5.07 Sec ), and have significant difference; results in pathology shows for mouse S group, the synaptophsion positive cell number of hippocampus CA1,CA3 and dentate gyrus are noticeably decreasing and the related IHS is 0.51±0.02, definitely lower than mouse SE and control Group (IHS for SE and control group: 2.06±0.07 and 2.03±0.34), which has significant difference. It means for mouse S group's synaptic structure of hippocampus neurons fiber terminal is damaged; compared with mouse SE and control Group, the mouse S group's Nissl's body within hippocampus neuron endochylema is decreasing and dying is lighter, which shows that the hippocampus neuron function of mouse S group is damaged. Meanwhile compared with mouse control group, behavior, synaptophysin's immunohistochemistry and Nissl's body for mouse SE have fewer differences.2. Group aged mouse: compared with mouse SE and control group, the ability of learning and memory for mouse S group is definitely decreasing. The time of passing water-maze are 49.86±26.35 Sec and 44.00±11.60 Sec,which have significant difference. Compare mouse SE with mouse control Group, the time of passing water-maze has no statistic significance. Histochemical stain shows synaptophysin immunoreactive positive cell IHS of the mouse S group is 0.40±0.02, which is clearly below mouse control group. However, synaptophysin immunoreactive positive cell IHS of mouse SE Group is 2.10±0.26, which is definitely over mouse control group (P<0.01), whose difference has significance ; compared with mouse S group , the Nissl's body in hippocampus neuron of mouse SE group is large, dense and hard dyed. There is no clear difference for mouse S and control group under common microscope.3. Compared with adult mouse and aged mouse in the corresponding group, the ability of learning and memory of aged mouse are definitely better than adult mouse. However the pathology shows that the number of immunoreactive positive cell of aged mouse S and control group is definitely lower than the corresponding adult mouse group, which has statistic significance. And the number of Nissl's body in the hippocampal neuron of aged mouse S and control Group is decreasing than that of adult mouse and the dying is light. However the results of synaptophysin histochemical stain and Nissl's body of aged mouse SE group are almost the same with that of adult mouse SE group. This shows that the function of hippocampus can be damaged by adverse stress, and this damage can extend to the old stage ; and the enriched environment can prevent and reverse this damage and slow down animals'aging.Conclusion: 1. Chronic adverse stress not only can damage adult mouse'current cognitive function but also this damage can last to the old stage.2. Chronic adverse stress and aging both can do harm to animals'cognitive function and both of them have synergistic action. And chronic stress can accelerate the process of aging.3. Enriched environment not only has curable function for brain damages resulted from various reasons but also has prevention function for handicap of cognitive function caused by chronic stress. And this function can last to animals'old stage and enriched environment can delay animals'aging.4. The present work adopts Nissl's body and synaptophysin as detection index which can reflect hippocampus neuron's function from all sides.
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