Objective  To explore different effects of chronic alcohol poisoning on cognition function of male and female mice and to reveal the change in mammalian target of rapamycin (mTOR) signaling pathway related proteins and the mechanism of brain injury induced by chronic alcohol poisoning.

  Methods  Totally 120 Kunming mice of 8-week old (half male and half female) were randomly assigned into low-, moderate-, and high-dose experimental groups with intragastric administration of 12.5%, 25%, and 50% ethanol at the dosage of 0.1 ml/10 g·day and a control group administrated with equal volume of distilled water. The administrations were applied once a day consecutively for 9 weeks. Then, learning and memory ability of the mice were determined with Morris water maze; relative expressions of phosphorylated mTOR (p-mTOR) and phosphorylated protein kinase B (p-Akt) in hippocampus of the mice were detected with Western blot.

  Results  Compared to those determined at the first day of Morris water maze test, the escape latency time (seconds) at the fifth day was significantly shortened for the mice of the control, low-, moderate-, and high-dose ethanol groups (for female mice: 24.49 ± 8.20 vs. 54.64 ± 5.23, 28.34 ± 9.88 vs. 55.22 ± 4.62, 29.13 ± 12.55 vs. 56.25 ± 3.43, and 34.46 ± 13.13 vs. 58.33 ± 0.85; for male mice: 24.46 ± 5.05 vs. 54.16 ± 3.91, 36.02 ± 9.17 vs. 55.69 ± 4.16, 38.76 ± 6.63 vs. 56.89 ± 2.80, 43.06 ± 8.06 vs. 58.34 ± 1.44, respectively) (P < 0.05 for all). In spatial probe trials, the female mice in high-ethanol group and the male mice in moderate-, and high-ethanol groups showed significantly lower travel distance (centimeters) in effective zone compared to the mice of control group (for the female mice: 20.88 ± 2.73 vs. 37.72 ± 1.78; for the male mice 20.19 ± 3.07 and 10.33 ± 3.07 vs. 37.65 ± 6.31) (P < 0.05 for all); for the mice of high-ethanol group, the males showed significantly lower travel distance in effective zone than the females (10.33 ± 3.07 vs. 20.88 ± 2.73) (P < 0.05). The results of Western blot revealed significantly higher expressions of p-Akt (2.75 ± 0.42) and p-mTOR (0.59 ± 0.10) in hippocampus only in the male mice of high-ethanol group compared to those (1.20 ± 0.51 and 0.34 ± 0.14) in the male mice of control group (both P < 0.05); while no significant differences in the expressions between the female mice of high-ethanol and control group.

  Conclusion  Gender differences exist in effects of chronic alcohol poisoning on learning and memory function of mice and mTOR signaling pathway may be involved in the process.