Abstract: Objective To study the mechanism of learning and memory impairment in aged female mice caused by chronic stress. Methods Twenty-month-old ICR mice were randomly divided into four groups: control females, control males, stressed females, and stressed males. Chronic stress was applied to the stress group for 30 days. The learning and memory ability was measured by novel object recognition test and Morris water maze test. Damage to hippocampal neurons was observed with Nissl staining, and dendrites of hippocampal neurons were observed with Golgi-Cox staining microscopy, the expression of the mammalian target of rapamycin (mTOR) and p-mTOR in hippocampal tissue was measured by Western blot, and the level of serum corticotropin-releasing hormone (CRH) was measured by ELISA. Results There was a significant decrease in the learning and memory ability only in the stressed female group after applied stress. In the Morris water maze, after a 6-day swimming training, the escape latency decreased in the control female group, the control male group and in the stressed male group(P＜0.001, P＜0.001, P＜0.05), but not in the stressed female group. The swimming speed was consistent across groups, but the number of platform crossings and the number of target quadrant crossings were significantly lower in the stressed female group than those in the control female and stressed male groups(P＜0.001).There was significant damage to neurons in the hippocampal CA3, CA1, and DG regions of mice in the stressed female group. The expression of hippocampal m-TOR and p-mTOR protein was significantly decreased in the stressed female group of mice(P＜0.05). In addition, chronic stress caused a significant increase in serum CRH levels in aged female mice(P＜0.05). Conclusions Chronic stress caused learning and memory impairment and pathological damage of the hippocampus in aged female mice, but not in aged male mice, which may be related to a fact that chronic stress elevates CRH and inhibits the hippocampal m-TOR signaling pathway in aged female mice.

Key words: chronic stress, memory impairment, m-TOR, p-mTOR, CRH