Ethanol-induced cognitive dysfunction is associated with alterations in the mammalian target of rapamycin signalling pathway in the hippocampus of male mice.

Abstract

The aim of the present study is to investigate the effect of acute excessive administration of ethanol on the expression of proteins related to the PI3K/Akt/mTOR signalling pathway in the mouse hippocampus and to reveal the possible molecular mechanism of learning and memory deficits induced by ethanol. A total of 120 8-week-old Kunming mice (half male and half female) were randomly assigned into low-dose, moderate-dose, and high-dose male and female groups with intragastric administration of 12.5, 25 and 50% ethanol, respectively, at the dosage of 0.1 ml/10 g·day for 14 days. The male and female control groups received an equal volume of distilled water. Then, the spatial learning and memory of the mice were evaluated by the Morris water maze task. The expression of p-mTOR, p-Akt, mTOR and Akt proteins was tested by western blotting and immunohistochemical staining methods in the hippocampal formation in each group, and haematoxylin-eosin stain was used to identify morphological changes in the hippocampal region. Our results indicated that 25 and 50% ethanol administration led to cognitive dysfunction and hippocampal pyramidal cell impairment in the female and male mice, with the male mice showing more severe impairment. In the 50% ethanol group, the male mice exhibited low expression levels of p-Akt and p-mTOR, but the female mice had no significant differences compared with the respective control group. Interestingly, the male expression levels of p-Akt and p-mTOR were significantly lower than those of females. Overall, these findings suggested that the cognitive deficits induced by ethanol are more serious in male mice than in female mice, and the PI3K/Akt/mTOR signalling pathway in the hippocampus might be involved in the impairment process.