Effects Of Acute And Chronic Stress On Spatial Learning And Memory Function And NT-3 In Brain

This study was to explore the changes in the spontaneous behavior and the ability of spatial learning-memory in mice of different ages after acute stress and chronic stress and the expression of neurotrophin-3(NT-3) in the brain. Using a foot shock(voltage 36 V, each lasting 30 s, 15 s each time interval, 30 times) to establish the model of acute stress animal, and chronic stress animal model which were established by seven kinds of stressors(foot shock, water deprivation, food deprivation, sleep deprivation, cold swimming, crowd, hathpace, randomly select one each day,21days). In new environment, through open-field test we examined the spontaneous activities and the exploratory behaviors. Morris water maze was adopted to test the ability of spatial learning memory of mice. In the hippocampus(HP) and prefrontal cortex(PFC) of mice, the changes of morphological structure were observed by HE staining, and using immunohistochemical method to detect the expression of NT-3.Results :1. Compared with the young control group mice, after acute stress immediately, the number of rearing and square crossing of young stress group mice increased significantly, and the defecation and central cell residence time were significantly reduced, however, the number of modification had no obvious changes. The 7th day after acute stress, the behavioral indicators of young mice in each group had no significant difference. After stress instantly and the 7th day after stress, in open-field test, the changing trends of aged stress group mice were consistent with young stress group.The aged control group mice were significantly less than the young control group mice on the rearing number.2. After acute stress immediately, the mice of young and aged stress group, their escape latency in the place navigation test were remarkably shortened, respectively compared with the young and aged control group mice. And the escape latency of aged control and stress group mice were obviously prolonged, compared with young group mice respectively. The 7th day after stress, comparing each group’s escape latency, the difference between the stress group mice and control group mice was not statistically significant.In the spatial search test, compared with respective young and aged control group mice after acute stress instantly, in first quadrant(i.e. platform quadrant) the swimming time of young and aged stress group mice were remarkably prolonged. Compared with young control group mice,the aged control group’s swimming time had no significant difference in first quadrant. The 7thday after stress, there was no significant deference between the stress group mice and control group mice.3. After acute stress instantly and 7th day after stress, respectively compared with young and aged control group mice, morphology of neurons in young and aged stress group mice didn’t change significantly.After acute stress immediately, the NT-3 positive cells number of stress group mice in HP and PFC were remarkably increased, and the average target gray value was significantly reduced.The expression of NT-3 in brain areas was significantly enhanced. Especially the young stress group mice changed significantly. The 7th day after stress, the difference of NT-3 expression in stress and control group mice was not significant. The expression of NT-3 in aged control mice was significantly lower than young control mice, and aged stress mice expressed significantly lower than young stress mice.4. Compared with the young control group mice, after chronic stress immediately, the number of square crossing, rearing and modification of young stress group mice were significantly decreased, both the defecation and central cell residence time were obviously increased. The 7th day after stress, the young stress mice’s number of square crossing, rearing and modification were still remarkably reduced. After chronic stress and the 7th day after stress,in open-field test, the aged stress group mice had the same trending with young stress group,especially the aged stress mice had more obvious changes.Compared with young control group mice, the rearing number and modification of aged control group were obviously reduced.5. After chronic stress and 7th day after stress, the young and aged stress group’s escape latency in the place navigation test were significantly higher than control group mice. And the escape latency of aged group mice was significantly prolonged, compared with young group mice.In the spatial search test, after chronic stress immediately, respectively compared with control group mice, in first quadrant(i.e. platform quadrant) the swimming time of young and aged stress group mice were obviously shortened. In first quadrant the swimming time of aged control group had no significant difference with young control group.6. After chronic stress instantly, the stress group mice showed obviously morphological changes in HP and PFC, such as the neurons number reducing, a loose arrangement, most cells dyeing shallow, dyed uneven and some cells atrophy. Compared with young control group mice,the distribution of neurons in different brain regions of aged control group was sparsely, however,structure of the cells were complete and regularly arranged. And neurons injury of aged stress group mice was much more serious than young stress group mice, and after 7th day after stress,there was still no significant recovery.After chronic stress immediately, the NT-3 positive cells number of stress group mice’s HP and PFC were remarkably reduced, however the average target gray value was obviously increased. The NT-3 expression of every brain regions were significantly reduced. The aged stress group mice’s expression changes were particularly significant. The expression of NT-3 in aged control mice was significantly lower than young control mice, and aged stress mice expressed significantly lower than young stress mice.Conclusion:1. As mice grow older, in the new environment the spontaneous behaviors and activities of exploration were significantly reduced, and the spatial learning-memory ability of mice was failing.2. The acute stress can enhance the spontaneous behaviors of mice, and significantly increase the spatial learning-memory ability of mice. However, the chronic stress weaken the spontaneous behaviors of mice, and the spatial learning-memory ability of mice was significantly impaired, aged mice was impaired more seriously.3. The acute stress did not cause significant changes in neuronal morphology of mice,however, in HP and PFC of mice brain, the chronic stress resulted significant changes in neuronal morphology. Aged mice were impaired more apparent.4. The acute stress can significantly up-regulate the expression of NT-3 in HP and PFC of mice brain. And the chronic stress obviously reduce expression of NT-3 in HP and PFC of mice brain.5. The aging brain of mice and the spatial learning-memory ability is closely correlated with the expression changes of NT-3.