A novel BOX maze learning paradigm measures sleep-induced cognitive impairment

Thesis (Master's)--University of Washington, 2019Sleep deprivation-induced cognitive impairment is a major health concern in developed countries and is an age-related risk factor for neurological conditions such as dementia associated with Alzheimer’s disease. There is an urgent need to develop ways of preventing the adverse neurological effects of sleep deprivation, but current preclinical cognitive assessments are highly time intensive with constant monitoring and at times generating data difficult to translate clinically. In this regard, a single day assay that focused just on assessing learning behavior in a time-effective and relatable manner would be of value. This report describes validation of the BOX maze as a behavioral paradigm for learning impairment in short-term sleep deprivation studies in mice. C57BL6 and C57BL/6xBALBc F1 (CB6F1) mice of both genders and varying ages were sleep deprived for 4 hours a day for 4 days, and then tested with the BOX maze. In some experiments, mice were treated with rapamycin daily during the 4 days of sleep deprivation. Sleep deprived mice showed learning impairment in an age, gender and strain dependent manner. The data provide evidence that the BOX maze is a behavioral paradigm that can be used to test short term sleep-deprivation induced learning impairment in young, middle, and older aged C57BL/6 and CB6F1 mice of both genders. B6 female mice, 22 months of age, treated with rapamycin showed significant improvement in learning time suggesting the BOX maze could be a useful behavioral assessment in sleep deprivation drug studies. In conclusion, the BOX maze could be used as an initial cognitive screening assay, or to complement other commonly used mouse behavioral assays