title: Inhibition of hippocampal neurogenesis by sleep deprivation is independent of circadian disruption and melatonin suppression.
abstract: Procedures that restrict or fragment sleep can inhibit neurogenesis in the hippocampus of adult rodents, although the underlying mechanism is unknown. We showed that rapid-eye-movement (REM) sleep deprivation (RSD) by the platform-over-water method inhibits hippocampal cell proliferation in adrenalectomized rats with low-dose corticosterone clamp. This procedure also greatly disrupts daily behavioral rhythms. Given recent evidence for circadian clock regulation of cell proliferation, we asked whether disruption of circadian rhythms might play a role in the anti-neurogenic effects of sleep loss. Male Sprague-Dawley rats were subjected to a 4-day RSD procedure or were exposed to constant bright light (LL) for 4 days or 10 weeks, a non-invasive procedure for eliminating circadian rhythms of behavior and physiology in this species. Proliferating cells in the granule cell layer of the dentate gyrus were identified by immunolabeling for the thymidine analogue 5-bromo-2-deoxyuridine. Consistent with our previous results, the RSD procedure suppressed cell proliferation by ∼50%. By contrast, although LL attenuated or eliminated daily rhythms of activity and sleep-wake without affecting daily amounts of REM sleep, cell proliferation was not affected. Melatonin, a nocturnally secreted neurohormone that is inhibited by light, has been shown to promote survival of new neurons. We found that 3-weeks of LL eliminated daily rhythms and decreased plasma melatonin by 88% but did not significantly affect either total cell survival or survival of new neurons (doublecortin+). Finally, we measured cell proliferation rates at the beginning and near the end of the daily light period in rats entrained to a 12:12 light/lark (LD) cycle, but did not detect a daily rhythm. These results indicate that the antineurogenic effect of RSD is not secondary to disruption of circadian rhythms, and provide no evidence that hippocampal cell proliferation and survival are regulated by the circadian system or by nocturnal secretion of pineal melatonin.
authors.affiliation: Department of Psychology, Simon Fraser University, Burnaby, BC, Canada V5A 1S6.
authors.forename: A D
authors.initials: AD
authors.lastname: Mueller
authors.forename: R J
authors.initials: RJ
authors.lastname: Mear
authors.forename: R E
authors.initials: RE
authors.lastname: Mistlberger
mesh_terms: D000315:Adrenalectomy; D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D002940:Circadian Rhythm / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004569:Electroencephalography; D006624:Hippocampus / Q000503:physiopathology*; D008027:Light / Q000009:adverse effects; D008297:Male; D008550:Melatonin / Q000097:blood*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity; D055495:Neurogenesis / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012892:Sleep Deprivation / Q000097:blood* / Q000473:pathology*; D012894:Sleep Stages / Q000502:physiology; D013997:Time Factors
chemical_list: C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D001973:Bromodeoxyuridine; D008550:Melatonin; D003345:Corticosterone