title: The inhibitory effect of sleep deprivation on cell proliferation in the hippocampus of adult mice is eliminated by corticosterone clamp combined with interleukin-1 receptor 1 knockout.
abstract: Deprivation or fragmentation of sleep for longer than 2days significantly inhibits cell proliferation and neurogenesis in the hippocampus of adult rats and mice. Signaling pathways that mediate these effects have yet to be clarified. Although deprivation procedures can stimulate adrenal corticosterone (CORT) release, suppression of cell proliferation by sleep deprivation does not require elevated CORT. We examined a role for interleukin-1β (IL-1β), a pro-inflammatory cytokine that is increased by sleep loss and that mediates effects of stress on hippocampal neurogenesis. Wild type (WT) and IL-1 receptor 1 knockout (IL1RI-KO) mice were subjected to rapid-eye-movement sleep deprivation (RSD) for 72-h using the multiple platform-over-water method. Mice were administered BrdU (100mg/kg) i.p. at hour 70 of RSD and were sacrificed 2-h later. New cells were identified by immunoreactivity (ir) for BrdU and Ki67 in the granular cell layer/subgranular zone (GCL/SGZ) and the hilus. In Experiment 1, WT and IL1RI-KO mice, by contrast with respective control groups, exhibited significantly fewer BrdU-ir and Ki67-ir cells. In Experiment 2, WT and IL1RI-KO mice were adrenalectomized (ADX) and maintained on constant low-dose CORT by osmotic minipumps. RSD reduced cell proliferation by 32% (p<0.01) in ADX-WT animals but did not significantly reduce proliferation in ADX IL1RI-KO animals (p>0.1). These results imply that RSD suppresses cell proliferation by the presence of wake-dependent factors (either elevated CORT or IL-1β signaling are sufficient), rather than the absence of a REM sleep-dependent process. The generality of these findings to other sleep deprivation methods and durations remains to be established.
authors.affiliation: Cognitive and Neural Sciences Program, Department of Psychology, Simon Fraser University, Burnaby, BC V5A1S6, Canada.
authors.forename: Anka D
authors.initials: AD
authors.lastname: Mueller
authors.forename: Maksim
authors.initials: M
authors.lastname: Parfyonov
authors.forename: Ilia
authors.initials: I
authors.lastname: Pavlovski
authors.forename: Elliott G
authors.initials: EG
authors.lastname: Marchant
authors.forename: Ralph E
authors.initials: RE
authors.lastname: Mistlberger
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003345:Corticosterone / Q000097:blood / Q000502:physiology*; D006624:Hippocampus / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055495:Neurogenesis; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D012892:Sleep Deprivation / Q000503:physiopathology*; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D017472:Receptors, Interleukin-1; D003345:Corticosterone
keywords: BrdU; Cell proliferation; Corticosterone; Hippocampus; Interleukin-1-β; Ki67; Rapid-eye-movement sleep deprivation