Submitted on November 30, 2007
Accepted on February 18, 2008
Sleep deprivation can inhibit adult hippocampal neurogenesis independent of adrenal stress hormones
Anka Mueller1, Michael S Pollock1, Stephanie E Lieblich2, Jonathan R Epp2, Liisa A.M. Galea3, and Ralph E Mistlberger1*
1 Psychology, Simon Fraser University, Burnaby, Canada
2 Psychology, University of British Columbia, Vancouver, Canada
3 United States; Psychology, University of British Columbia, Vancouver, Canada
* To whom correspondence should be addressed. E-mail: mistlber{at}sfu.ca.
Sleep deprivation (SD) can suppress cell proliferation in the hippocampal dentate gyrus of adult male rodents, suggesting that sleep may contribute to hippocampal functions by promoting neurogenesis. However, suppression of cell proliferation in rats by the platform-over-water SD method has been attributed to elevated corticosterone (CORT), a potent inhibitor of cell proliferation and non-specific correlate of this procedure. We report here results that do not support this conclusion. Intact and adrenalectomized (ADX) male rats were subjected to a 96-h SD using multiple and single platform methods. New cells were identified by immunoreactivity for 5-bromo-2-deoxyuridine (BrdU) or Ki67, and new neurons by immunoreactivity for BrdU and doublecortin. EEG recordings confirmed a 95% deprivation of REM sleep and 40% decrease of non-REM sleep. Cell proliferation in the dentate gyrus was suppressed by up to 50% in sleep-deprived rats relative to apparatus control or home cage control rats. This effect was also observed in ADX rats receiving continuous low-dose CORT replacement via subcutaneous minipumps, but not in ADX rats receiving CORT replacement via drinking water. In these latter rats, CORT intake via water was reduced by 60% during SD; upregulation of cell proliferation by reduced CORT intake may obscure inhibitory effects of sleep loss on cell proliferation. SD had no effect on the percentage of new cells expressing a neuronal phenotype. These results demonstrate that the CORT replacement method is critical for detecting an effect of sleep deprivation on cell proliferation, and support a significant role for sleep in adult neurogenesis.
