Sleep-deprived cognitive impairment in aging mice is alleviated by rapamycin

Abstract

Objective: Sleep deprivation-induced cognitive impairment is a major health concern and an age-related risk factor for dementia. There is an urgent need to develop ways of preventing the adverse neurological effects of sleep deprivation, but current preclinical animal models of short-term sleep deprivation are not well described.

Methods: C57BL6 mice of varying ages were sleep deprived for 4 hours a day for 4 days, and then tested with a Box maze navigation task.

Results:  Sleep deprived mice at young, middle and older ages showed learning impairment that varied by strain and gender. In general, females of both strains were more sensitive to sleep deprivation than males. To determine whether sleep deprivation-induced learning impairment would respond to therapeutic intervention, an independent cohort of mice was treated with rapamycin daily during the 4 days of sleep deprivation. Mice that were sleep deprived and treated with rapamycin showed significant improvement in learning time suggesting that the cognitive impairment might be associated in part with molecular and cellular mechanisms targeted by rapamycin.

Conclusions: The observations from this study suggest that aging mice would be productive models to study pathobiology and therapeutic intervention of cognitive impairment triggered by age-related sleeping disorders in people.