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

doi:10.1016/j.neuroscience.2010.08.018

Neuroscience

Volume 170, Issue 4, 10 November 2010, Pages 1140-1152

https://doi.org/10.1016/j.neuroscience.2010.08.018 Get rights and content

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.

Section snippets

Animals

All experiments were carried out in accordance with the guidelines of the Canadian Council on Animal Care and all protocols involving animals were approved by the Dalhousie University Committee on Laboratory Animals. Two-month-old adult male Sprague–Dawley rats weighing 225–250 g were obtained from Charles River Canada (St. Constant, QC, Canada) and kept in standard housing cages with food (Agribrands Purina rat chow) and water available ad libitum under a 12:12 h light:dark cycle, with lights

Experiment 1—immunohistochemical comparison of three markers for cell proliferation

To determine how effectively the current protocols for Ki67 and PCNA immunolabeling identified their respective proliferating cell populations, we examined the extent of double labeling for each intrinsic marker with BrdU in the dentate gyrus of the hippocampus. S-phase occupies ∼9.5 h out of a ∼25 h cell cycle (∼38% of the total time) according to estimates by Cameron and McKay (2001) for adult rat hippocampal progenitor cells. Assuming that a 2 h window for BrdU incorporation labels all

Discussion

The results obtained using BrdU injections 2 h before the end of SD (Experiment 2) indicated a biphasic effect of 6–48 h SD on BrdU-labeling in the adult rat hippocampus, with an initial increase at 12 h SD followed by a trend toward a decrease at 48 h. Surprisingly, 6–48 h SD had no effect on the expression of the intrinsic cell proliferation markers Ki67 and PCNA. We used an additional 10 h BrdU injection paradigm to clarify the effects of 12 h SD on cell proliferation (Experiment 3), which

Conclusion

In conclusion, assessing hippocampal cell proliferation with multiple strategies allowed us to differentiate an acceleration of cell proliferation after 12 h SD from an increase in the total number of progenitor cells. The literature on regulation of cell proliferation contains few reports on changes in cell cycle dynamics, perhaps because of the usual reliance on BrdU labeling as a measure of cell proliferation. More evidence for changes in cell cycle dynamics in response to physiological

Acknowledgments

We thank Joan Burns and Donna Goguen for technical assistance, Ilya Pavlovski and Elizabeth Cumyn for assisting with animal handling and injections, and Lisa Wright and Tara Perrot-Sinal for assistance with corticosterone assays. This work was funded by CIHR grant MOP-67085 and graduate scholarships from CIHR and the Killam Trust (AJ).

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For example, while finding no evidence for proliferation in the subgranular zone after 24 h sleep disruption, a decrease in ki-67+ cell numbers in the hilus was observed after 24 h, without a change in BrdU+ cells (Roman et al., 2005). The hilus is not a known location of neurogenesis, but has been suggested to be a location of gliogenesis (Steiner et al., 2004), suggesting that sleep disruption may effect glial cell proliferation and not neuronal cell proliferation within the first 24 h. Two studies have found significantly increased numbers of BrdU+ cells after 12 h of sleep loss by gentle handling (Grassi Zucconi et al., 2006) and forced activity (Junek et al., 2010). Interestingly, the number of BrdU+ cells remained elevated 15 and 30 days after the one sleep loss exposure (Grassi Zucconi et al., 2006).
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Cognitive, Behavioral, and Systems NeuroscienceResearch PaperShort-term sleep deprivation may alter the dynamics of hippocampal cell proliferation in adult rats

Abstract

Section snippets

Animals

Experiment 1—immunohistochemical comparison of three markers for cell proliferation

Discussion

Conclusion

Acknowledgments

Accid Anal Prev

Neurosci Lett

Neurobiol Aging

Neuroscience

Biol Psychol

Brain Res Dev Brain Res

Neurosci Biobehav Rev

Sleep Med Rev

Brain Res Bull

Neuroscience

Biochem Biophys Res Commun

Neuroscience

J Neurosci Methods

Trends Neurosci

Neurosurg Clin N Am

J Chem Neuroanat

Neuroscience

Sleep Med Rev

Neurosci Lett

Brain Res

Neurosci Lett

Neuroscience

Brain Res

Behav Brain Res

J Biol Chem

The histaminergic system in the guinea pig central nervous system: an immunocytochemical mapping study using an antiserum against histamine

J Comp Neurol

Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats

J Comp Neurol

Chromatin-bound PCNA complex formation triggered by DNA damage occurs independent of the ATM gene product in human cells

Nucleic Acids Res

Patterns of performance degradation and restoration during sleep restriction and subsequent recovery: a sleep dose-response study

J Sleep Res

Sleep deprivation in the rat: V. Energy use and mediation

Sleep

Effects of overnight sleep restriction on brain chemistry and mood in women with unipolar depression

J Psychiatry Neurosci

Effects of adrenalectomy and subsequent corticosterone replacement on rat sleep state and EEG power spectra

Am J Physiol

Existence of two populations of cyclin/proliferating cell nuclear antigen during the cell cycle: association with DNA replication sites

J Cell Biol

Serotonin may stimulate granule cell proliferation in the adult hippocampus, as observed in rats grafted with foetal raphe neurons

Eur J Neurosci

Transient expression of doublecortin during adult neurogenesis

J Comp Neurol

Cell cycle dependent expression and stability of the nuclear protein detected by Ki-67 antibody in HL-60 cells

Cell Prolif

Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus

J Comp Neurol

Cognitive, Behavioral, and Systems Neuroscience
Research Paper
Short-term sleep deprivation may alter the dynamics of hippocampal cell proliferation in adult rats