| Using stress animal model of multivariate chronic unpredictable stressors (food deprivation, water deprivation, cold stimulation, bondage+hot stimulus, foot shock, hathpace, bondage,one method each day for 21 days), and aging animal model which were established by subcutaneous injection of D-galactose (100mg/kg·d-1 for 42 days) in this study, we examined the spontaneous behaviors of mice in new environment by open field test, and the ability of spatial learning memory of mice by Morris water maze. The changes of morphological structure in hippocampus (HP) and prefrontal cortex (PFC) of mice brain were observed by HE dye, and the expression of GDNF in HP and PFC were detected by immunohistochemical method. This study aims to investigate the effects of chronic stress on the spontaneous behaviors and ability of spatial learning-memory in different aged and aging model mice, and its mechanism.The results of this study are as follows:1. After stress immediately, compared with the young control group mice, the square crossing, rearing and grooming of young stress group mice were remarkably decreased, and the central cell residence time and defecation were significantly increased. The 7th day after stress, compared with the young control group mice, the square crossing and rearing of the young stress group mice were remarkably decreased, and the central cell residence time was significantly increased. After stress and the 7th day after stress, aged stress group mice had more remarkable changes in square crossing, rearing, grooming and the central cell residence time than the young stress group mice.After stress immediately, compared with the young control group mice, the rearing and grooming of the aged control group mice were remarkably decreased, and the central cell residence time was significantly increased.2. In the place navigation test, after stress immediately and 7th day after stress, compared with the young and aged control group mice, the escape latency to find platform of the young and aged stress group mice were significantly increased, respectively. Compared with the young group mice, the escape latency of the aged control and stress group mice were significantly increased.In the space probe test, compared with the young and aged control group mice, the swimming time in target quadrant of the young and aged stress group mice were remarkably decreased after chronic stress, respectively. There were no significant differences in swimming time between the young and aged control group mice.3. The stress group mice displayed obviously morphologic changes such as cell imperfection, intercellular space broaden, cell atrophy, and cell dyed uneven, the most were dyed shallowly in HP and PFC after stress and 7th day after stress. Compared with the young control group mice, the aged stress group mice showed more cell imperfection after stress immediately and 7th day after stress.4. Immunohistochemical analysis results showed that compared with the control group mice, the number of GDNF positive neurons of HP and PFC were significantly reduced, and the average target gray value were remarkably increased in the stress group mice after stress, and the changes were still on 7th day after stress. The aged control and stress group mice showed lower GDNF expression in HP and PFC than the young control and stress mice after stress immediately and 7th day after stress.5. After stress immediately, compared with the control group mice, the square crossing, rearing and grooming of the aging model group mice were remarkably decreased, and the central cell residence time and defecation were significantly increased. Compared with the aging model group mice, the quare crossing, rearing and grooming of the aging model stress group mice were remarkably increased, and the central cell residence time and defecation were significantly decreased.6. In the place navigation test, compared with the control group mice, the escape latency to find platform of the aging model group mice was significantly increased after stress immediately. Compared with the aging model group mice, the escape latency of the aging model stress group mice were significantly decreased.In the space probe test, compared with the control group mice, the swimming time in target quadrant of the aging model group mice was remarkably decreased after stress immediately. Compared with the aging model group mice, the swimming time in target quadrant of the aging model stress group mice were significantly increased.7. The aging model group mice displayed obviously morphologic changes such as cell imperfection, intercellular space broaden, cell swelling and atrophy, and cell dyeing uneven, most dyeing shallow in HP and PFC after stress immediately. There were no remarkable changes in the morphologic structure between the control group and the aging model stress group mice.8. The number of GDNF positive neurons of HP and PFC was significantly reduced, and the average target gray value was remarkably increased in the aging model group mice after stress, and the changes were gradually returned on 7th day after stress. Compared with the aging model group mice, the aging model stress group mice showed higher GDNF expression in HP and PFC. The 7th day after stress, compared with the control group, the aging model group mice showed the GDNF expression in HP and PFC returned gradually. Conclusion:1. Accompany with the growth of the age, the spontaneous behaviors and the spatial learning-memory ability of mice was significantly reduced; and it is more evident under conditions of chronic stress. The aged group mice had more serious abnormal of behaviors after chronic stress.2. The chronic stress caused obvious morphological changes of neurons in HP and PFC of mice brain, and significant reduction of GDNF expression in HP and PFC. The aged group mice showed more seriously cell imperfection.3. D-galactose could induced significantly damage in the spontaneous behaviors and the spatial learning-memory ability of mice, and caused obvious morphological changes of neurons in HP and PFC of mice brain, and induced significant reduction of GDNF expression in HP and PFC. However the aging group mice had better behavior and GDNF expression after chronic stress.4. The brain aging and the changes of the spatial learning-memory ability which may be nearly related to the expression of GDNF in HP and PFC. |
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