The Effect Of Surgical And Psychological Stress On Learning And Memory Function In Aged Mice

Postoperative cognitive dysfunction (POCD) is an important complication following major surgery and general anesthesia in older patients. Patients are suffering physically and pshchologically during the perioperative period. There is emerging evidence that the surgery could lead to cognitive impairment. However, it is still unknown that how will the perioperative psychological stress affect cognition in the older patients. In this study, we aimed to investigate the effect of surgical and psychological stress on learning and memory function and its underlying mechanisms in aged C57 mice.Part I The effect of surgical and psychological stress on learning and memory function in aged miceObjective:To investigate the effect of surgical stress, psychological stress and psychological stress plus surgical stress on learning and memory in aged C57 mice.Methods:Aged female C57 mice were randomly asssigned to 3 groups: surgical stress (Group S, n=32), psychological stress (Group P, n=32) and combine stress (Group X, n=32). There are 2 subgroups within each group: treatment (Subgroup T, n=16) and control (Subgroup C, n=16). The mice in group ST were subjected to exploratory laparotomy under local anesthesia, while group SC received sham surgery. The mice in group PT were subjected to psychological stress induced by a communication box for 15 consecutive days, while group PC received sham psychological stress. The mice in group XT were subjected to first psychological and then surgical stress described above, while group XC received both sham psychological stress and surgery. Cognitive functions were assessed at 1,3 and 7 days following the stress.Results:1. Compared to the mice in group SC and group XC, the mice in group ST and group XT had a longer escape latency and a lower discrimination index.2. There were no difference in the cognitive function between group PT and group PC.3. No difference in learning and memory were found between group ST and group XT.Conclusion:Psychological stress is not a constitutive factor of POCD. Peripheral abdominal surgical stress leads to POCD in aged mice.Part II The underlying mechanism of the alteration of cognitive function due to surgical and psychological stress in aged mice.Objective:To investigate the underlying mechanisms of the alteration of cognitive function due to surgical and psychological stress in aged C57 mice.Methods:Aged female C57 mice were randomly asssigned to 3 groups: surgical stress (Group S, n=36), psychological stress (Group P, n=36) and combine stress (Group X, n=36). There are 2 subgroups within each group: treatment (Subgroup T, n=18) and control (Subgroup C, n=18). The mice in group ST were subjected to exploratory laparotomy under local anesthesia, while group SC received sham surgery. The mice in group PT were subjected to psychological stress induced by a communication box for 15 consecutive days, while group PC received sham psychological stress. The mice in group XT were subjected to first psychological and then surgical stress described above, while group XC received both sham psychological stress and surgery.Number of neurons and markers of the AKT/mTOR pathway were assessed at 1,3 and 7 days following the stress.Results:1. The number of neurons in the CA1 region of the hippocampus of the mice in group ST and group XT were significantly lower than the other groups at day 7 after the stress.2. The plasma TNF-a in group ST and XT were elevated at day 1 after the stress.3. The expression of p-AKT in the hippocampus of the mice in group ST and group XT were suppressed at day 1 and day 3 following the stress, whereas the p-AKT in the cortex were not affected.4. At day 3 after the stress treatment, the expression of p-mTOR in both the hippocampus and the cortex were suppressed in group ST and group XT.5. The expression of p-PKCa in both the hippocampus and the cortex were elevated in all the treatment subgroups at day 1 after the stress, but within 2 days were apparently back to normal.Conclusion:The disturbance of AKT/mTOR pathway and the decrease of number of neurons are likely involved as underlying mechanisms of the alteration of cognitive function due to surgical and psychological stress in aged C57 mice.