Short-term sleep deprivation may alter the dynamics of hippocampal cell proliferation in adult rats

Abstract

Long-term (>48 h) sleep deprivation (SD) reduces adult rat hippocampal cell proliferation and neurogenesis, yet reported effects of short-term (<24 h) SD are inconsistent. We systematically assessed the effects of various durations of SD on adult rat hippocampal cell proliferation. Rats were sleep-deprived for 6, 12, 24, 36 or 48 h and injected with 5-bromo-2'-deoxyuridine (BrdU) 2 h before the end of SD. Immunolabeling for BrdU in the hippocampal subgranular zone increased significantly after 12 h SD but tended to decrease after 48 h SD relative to respective Controls. Surprisingly, SD did not alter immunolabeling for Ki67 protein (Ki67) or proliferating cell nuclear antigen (PCNA), two intrinsic cell proliferation markers. SD did not affect BrdU or Ki67 labeling in the subventricular zone, nor did it affect serum corticosterone levels. Because immunoreactivity for Ki67 and PCNA can identify cells in all phases of the ∼25 h cell cycle in adult rat hippocampus, whereas BrdU labels only cells in S-phase (∼9.5 h), this discrepancy suggests that 12 h SD might have affected cell cycle dynamics. A separate group of rats were injected with BrdU 10 h before the end of 12 h SD, which would allow some time for labeled cells to divide; the results were consistent with an acceleration of the timing of hippocampal progenitor cell division during 12 h SD. These results suggest that short-term (12 h) SD transiently produces more hippocampal progenitor cells via cell cycle acceleration, and confirm the importance of using multiple cell cycle markers or BrdU injection paradigms to assess potential changes in cell proliferation.