Appropriate Rest Time after Repetitive Sleep Deprivation Suppresses Apoptosis and Cell Proliferation in the Hippocampus

ABSTRACT

PURPOSE: Sleep deprivation may exert many negative effects on hippocampus-dependent cognitive function, such as learning and memory. The present study was conducted in order to investigate the effects of repetitive sleep deprivation on cognition, apoptotic neuronal cell death, and cell proliferation in the hippocampus, using mice. METHODS: To induce sleep deprivation, mice were placed in a water cage containing six platforms (3 cm in diameter), surrounded by water up to 1 cm beneath the surface of the platform for 24 h. Mice were randomly divided into four groups (n=20 in each group): control group, 24 h rest after 24 h sleep deprivation group, 48 h rest after 24 h sleep deprivation group, and 72 h rest after 24 h sleep deprivation group. This cycle was continued for 36 days. Novel objective recognition test and immunohistochemistry for 5-bromo-2'-deoxyuridine (BrdU), western blot for expression of Bax, Bcl-2, brain-derived neurotrophic factor (BDNF), and caspase-3 were performed. RESULTS: Results of the novel objective recognition test showed decreased cognition in the 24 h rest after 24 h sleep deprivation group, while a similar effect was observed in other groups, compared to the control group. Increased cell proliferation and enhanced expression of BDNF and Bax protein were observed in the 24 h rest after 24 h sleep deprivation group and the 48 h rest after 24 h sleep deprivation group, compared to the control group. Expression of Bcl-2 showed a decrease in the 24 h and 48 h rest groups, compared to the control group. Expression of caspase-3 in the dentate gyrus of the hippocampus showed a significant increase in the 24 h rest after 24 h sleep deprivation group and in the 48 h rest after 24 h sleep deprivation group, compared to the control group. CONCLUSION: Results of the present study indicate that insufficient rest after sleep deprivation may induce impairment of cognitive function. After sleep deprivation, at least 72 hr of rest time is needed for recovery.