Sleep restriction by forced activity reduces hippocampal cell proliferation

Mounting evidence suggests that sleep loss negatively affects learning and memory processes through disruption of hippocampal function. In the present study, we examined whether sleep loss alters the generation, differentiation, and survival of new cells in the dentate gyrus. Rats were sleep restricted by keeping them awake in slowly rotating drums for 1 day or repeatedly for 20 h/day over a period of 8 days. In addition to home cage controls, we included forced activity controls which, compared to sleep restricted rats, walked at double speed for half the time. These animals thus walked the same distance but had sufficient time to sleep. The results show that a single day of sleep deprivation significantly reduced hippocampal cell proliferation in the hilus of the dentate gyrus as measured by immunostaining for the proliferation marker Ki-67. Repeated partial sleep deprivation reduced cell proliferation in both the hilus and the subgranular zone. However, the latter was also found after chronic forced activity, and may not have been specific for sleep loss. To study neuronal survival, rats received a single intraperitoneal injection of 5-bromo-2′-deoxyuridine (BrdU) 5 days before the experiment. The number of surviving, BrdU-positive cells was not affected by sleep restriction. Also, the differentiation of BrdU-positive new cells into NeuN-positive neuronal and GFAP-positive glial phenotypes was not significantly altered by sleep loss. In conclusion, since new cells in the hilus mostly differentiate into glia, our findings indicate that sleep loss may reduce hippocampal gliogenesis.