Sleep Deprivation Reduces Proliferation of Cells in the Dentate Gyrus of the Hippocampus in Rats

The dentate gyrus (DG) of the adult hippocampus gives rise to progenitor cells, which have the potential to differentiate into neurons. To date it is not known whether sleep or sleep loss has any effect on proliferation of cells in the DG. Male rats were implanted for polysomnographic recording, and divided into treadmill sleep‐deprived (SD), treadmill control (TC) and cage control (CC) groups. SD and TC rats were kept for 96 h on a treadmill that moved either for 3 s on/12 s off (SD group) or for 15 min on/60 min off (TC group) to equate total movement but permit sustained rest periods in TC animals. To label proliferating cells the thymidine analogue 5‐bromo‐2′‐deoxyuridine (BrdU) was injected after the first 48 h of the experimental procedure in all groups (50 mg kg−1, i.p.). The percentage of time awake per day was 93.2 % in the SD group vs. 59.6 % in the TC group and 49.9 % in the CC group (P < 0.001). Stereological analysis showed that the number of BrdU‐positive cells in the DG of the dorsal hippocampus was reduced by 54 % in the SD group in comparison with the TC and by 68 % in comparison with the CC group. These results suggest that sleep deprivation reduces proliferation of cells in the DG of the dorsal hippocampus.

[1]  S. MacNeill,et al.  ATP-dependent DNA ligases , 2002, Genome Biology.

[2]  C. Lois,et al.  Long-distance neuronal migration in the adult mammalian brain. , 1994, Science.

[3]  Allan I Pack,et al.  Rest in Drosophila Is a Sleep-like State , 2000, Neuron.

[4]  M. Stryker,et al.  Sleep Enhances Plasticity in the Developing Visual Cortex , 2001, Neuron.

[5]  M. Moser,et al.  Reduced fear expression after lesions of the ventral hippocampus , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[6]  F. Gage,et al.  Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus , 1999, Nature Neuroscience.

[7]  J. Conway,et al.  Brief Paradoxical Sleep Deprivation Impairs Reference, but Not Working, Memory in the Radial Arm Maze Task , 1998, Neurobiology of Learning and Memory.

[8]  Irene Tobler,et al.  Sleep deprivation modulates brain mRNAs encoding genes of glycogen metabolism , 2002, The European journal of neuroscience.

[9]  G. Brown,et al.  Cellular energy utilization and molecular origin of standard metabolic rate in mammals. , 1997, Physiological reviews.

[10]  Stanley J. Wiegand,et al.  Infusion of Brain-Derived Neurotrophic Factor into the Lateral Ventricle of the Adult Rat Leads to New Neurons in the Parenchyma of the Striatum, Septum, Thalamus, and Hypothalamus , 2001, The Journal of Neuroscience.

[11]  M. Moser,et al.  Functional differentiation in the hippocampus , 1998, Hippocampus.

[12]  H. Craig Heller,et al.  Restoration of brain energy metabolism as the function of sleep , 1995, Progress in Neurobiology.

[13]  H. Roffwarg,et al.  REM sleep deprivation in monocularly occluded kittens reduces the size of cells in LGN monocular segment. , 1998, Sleep.

[14]  R. McCarley,et al.  Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep: an in vivo microdialysis study , 2000, Neuroscience.

[15]  R. Murison,et al.  The effect of sleep deprivation and recovery sleep on plasma corticosterone in the rat , 1983, Neuroscience Letters.

[16]  A. Rechtschaffen,et al.  Sleep deprivation in the rat: X. Integration and discussion of the findings. , 2002, Sleep.

[17]  P. Eriksson,et al.  Peripheral Infusion of IGF-I Selectively Induces Neurogenesis in the Adult Rat Hippocampus , 2000, The Journal of Neuroscience.

[18]  Yvette I. Sheline,et al.  Depression Duration But Not Age Predicts Hippocampal Volume Loss in Medically Healthy Women with Recurrent Major Depression , 1999, The Journal of Neuroscience.

[19]  S. Rivkees,et al.  A1 adenosine receptor activation inhibits neurite process formation by rho kinase-mediated pathways , 2001, Neuroreport.

[20]  E. Markus,et al.  The Effects of Aging and Dorsal Hippocampal Lesions: Performance on Spatial and Nonspatial Comparable Versions of the Water Maze , 2002, Neurobiology of Learning and Memory.

[21]  R. Jordan,et al.  Circadian variation in the expression of cell-cycle proteins in human oral epithelium. , 1999, The American journal of pathology.

[22]  D. Abrous,et al.  Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[23]  T J Sejnowski,et al.  Running enhances neurogenesis, learning, and long-term potentiation in mice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[24]  F. Gage,et al.  Neurogenesis in the adult human hippocampus , 1998, Nature Medicine.

[25]  Neural plasticity to stress and antidepressant treatment , 1999, Biological Psychiatry.

[26]  P. Maquet,et al.  Sleep function(s) and cerebral metabolism , 1995, Behavioural Brain Research.

[27]  E. Gould,et al.  Neurogenesis in the adult is involved in the formation of trace memories , 2001, Nature.

[28]  M. Bunsey,et al.  Differential Effects of Dorsal and Ventral Hippocampal Lesions , 1998, The Journal of Neuroscience.

[29]  A. Rechtschaffen,et al.  Sleep deprivation in the rat: I. Conceptual issues. , 1989, Sleep.

[30]  H. Gundersen,et al.  Unbiased stereological estimation of the number of neurons in the human hippocampus , 1990, The Journal of comparative neurology.

[31]  J. Altman,et al.  Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats , 1965, The Journal of comparative neurology.

[32]  Mortimer Mamelak.  Neurodegeneration, Sleep, and Cerebral Energy Metabolism: A Testable Hypothesis , 1997, Journal of geriatric psychiatry and neurology.

[33]  A. Ruifrok,et al.  Diurnal variations in the expression of radiation-induced apoptosis. , 1998, Radiation research.

[34]  C. Smith,et al.  Posttraining paradoxical sleep in rats is increased after spatial learning in the Morris water maze. , 1997, Behavioral neuroscience.

[35]  J. Csernansky,et al.  Hippocampal atrophy in recurrent major depression. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[36]  M. Mishkin,et al.  Positive Correlations Between Cerebral Protein Synthesis Rates and Deep Sleep in Macaca mulatta , 1997, The European journal of neuroscience.

[37]  J. Krueger,et al.  Changes in sleep in response to intracerebral injection of insulin-like growth factor-1 (IFG-1) in the rat. , 1998, Sleep research online : SRO.

[38]  C. Gambelunghe,et al.  Effects of light physical exercise on sleep regulation in rats. , 2001, Medicine & Science in Sports & Exercise.

[39]  Michael S. Fanselow,et al.  Electrolytic Lesions of the Fimbria/Fornix, Dorsal Hippocampus, or Entorhinal Cortex Produce Anterograde Deficits in Contextual Fear Conditioning in Rats , 1997, Neurobiology of Learning and Memory.

[40]  C. Cotman,et al.  Exercise: a behavioral intervention to enhance brain health and plasticity , 2002, Trends in Neurosciences.

[41]  P. Rakic.  Progress: Neurogenesis in adult primate neocortex: an evaluation of the evidence , 2002, Nature Reviews Neuroscience.

[42]  G. Rose,et al.  Evidence for a paradoxical sleep window for place learning in the Morris water maze , 1996, Physiology & Behavior.

[43]  S. Inoué,et al.  Sleep as neuronal detoxification and restitution , 1995, Behavioural Brain Research.

[44]  L. Staib,et al.  Hippocampal volume reduction in major depression. , 2000, The American journal of psychiatry.

[45]  B. McEwen,et al.  Prolonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[46]  G. Tononi,et al.  Correlates of sleep and waking in Drosophila melanogaster. , 2000, Science.

[47]  P. Meerlo,et al.  Sleep Restriction Alters the Hypothalamic‐Pituitary‐Adrenal Response to Stress , 2002, Journal of neuroendocrinology.

[48]  H. Gundersen.  Stereology of arbitrary particles * , 1986, Journal of microscopy.

[49]  L. Swanson.  The Rat Brain in Stereotaxic Coordinates, George Paxinos, Charles Watson (Eds.). Academic Press, San Diego, CA (1982), vii + 153, $35.00, ISBN: 0 125 47620 5 , 1984 .

[50]  W. Greenough,et al.  Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[51]  Roland R Roy,et al.  Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. , 2002, Journal of neurophysiology.

[52]  Klaus P. Ebmeier,et al.  Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression , 1998, British Journal of Psychiatry.

[53]  J. Kesslak,et al.  Spatial learning and physical activity contribute to the induction of fibroblast growth factor: neural substrates for increased cognition associated with exercise , 1998, Neuroscience.

[54]  Eric J. Nestler,et al.  Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus , 2000, The Journal of Neuroscience.

[55]  F. Gage,et al.  Epidermal Growth Factor and Fibroblast Growth Factor-2 Have Different Effects on Neural Progenitors in the Adult Rat Brain , 1997, The Journal of Neuroscience.

[56]  R. Kirov,et al.  Distinct sleep-wake stages in rats depend differentially on age , 2002, Neuroscience Letters.

[57]  Kei Yamamoto,et al.  Differential effect of short-term REM sleep deprivation on NGF and BDNF protein levels in the rat brain , 2000, Brain Research.

[58]  R. McKay,et al.  Restoring production of hippocampal neurons in old age , 1999, Nature Neuroscience.

[59]  F. Gage,et al.  More hippocampal neurons in adult mice living in an enriched environment , 1997, Nature.

[60]  J. Krueger,et al.  Epidermal growth factor enhances spontaneous sleep in rabbits. , 1998, The American journal of physiology.

[61]  C. Bonardi.  Dorsal hippocampal lesions impair appetitive classical conditioning to localized cues , 2001, The European journal of neuroscience.

[62]  Fernando Nottebohm,et al.  Migration of young neurons in adult avian brain , 1988, Nature.

[63]  H. Gundersen,et al.  Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator , 1991, The Anatomical record.

[64]  E. Gould,et al.  Neurogenesis in the Dentate Gyrus of the Adult Tree Shrew Is Regulated by Psychosocial Stress and NMDA Receptor Activation , 1997, The Journal of Neuroscience.

[65]  J. Goldman,et al.  A clonal analysis of glial lineages in neonatal forebrain development in vitro , 1990, Neuron.

[66]  C. Dugovic,et al.  Sleep-wakefulness patterns in the helpless rat , 1991, Physiology & Behavior.

[67]  J. Hinds,et al.  Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. , 1977, Science.

[68]  B. Jacobs,et al.  Adult brain neurogenesis and psychiatry: a novel theory of depression , 2000, Molecular Psychiatry.

[69]  Peng Huang,et al.  The Circadian Gene Period2 Plays an Important Role in Tumor Suppression and DNA Damage Response In Vivo , 2002, Cell.

[70]  C. Guézennec,et al.  Exercise-induced changes in brain glucose and serotonin revealed by microdialysis in rat hippocampus: effect of glucose supplementation. , 2001, Acta physiologica Scandinavica.

[71]  F. Chaouloff.  Effects of acute physical exercise on central serotonergic systems. , 1997, Medicine and science in sports and exercise.

[72]  P. Rakić,et al.  Continuation of neurogenesis in the hippocampus of the adult macaque monkey. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[73]  R. McKay,et al.  Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus , 2001, The Journal of comparative neurology.

[74]  A. Pack,et al.  Brain Glycogen Decreases with Increased Periods of Wakefulness: Implications for Homeostatic Drive to Sleep , 2002, The Journal of Neuroscience.

[75]  D. Ryan,et al.  The Effects of Paradoxical Sleep Deprivation and Valine on Spatial Learning and Brain 5-HT Metabolism , 1999, Physiology & Behavior.

[76]  Richter Cp.  Sleep and activity: their relation to the 24-hour clock. , 1967 .

[77]  P. Andersen,et al.  Spatial learning impairment parallels the magnitude of dorsal hippocampal lesions, but is hardly present following ventral lesions , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[78]  A. Coenen,et al.  Stress induced by three procedures of deprivation of paradoxical sleep , 1985, Physiology & Behavior.

[79]  G. Tononi,et al.  No evidence of brain cell degeneration after long-term sleep deprivation in rats 1 Published on the World Wide Web on 8 July 1999. 1 , 1999, Brain Research.

[80]  Donna H. Ryan,et al.  Sleep Deprivation by the “Flower Pot” Technique and Spatial Reference Memory , 1997, Physiology & Behavior.

[81]  T. Palmer,et al.  Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[82]  V. Gurevich,et al.  The Nature of the Arrestin·Receptor Complex Determines the Ultimate Fate of the Internalized Receptor* , 2003, The Journal of Biological Chemistry.

[83]  J. Krueger,et al.  Brain-derived neurotrophic factor enhances spontaneous sleep in rats and rabbits. , 1999, American journal of physiology. Regulatory, integrative and comparative physiology.

[84]  H. Haas,et al.  Extracellular adenosine levels in neostriatum and hippocampus during rest and activity periods of rats , 1996, Neuroscience.

[85]  R. McCarley,et al.  Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness. , 1997, Science.

[86]  A. Rechtschaffen,et al.  Effects of method, duration, and sleep stage on rebounds from sleep deprivation in the rat. , 1999, Sleep.

[87]  C. P. Richter.  Sleep and activity: their relation to the 24-hour clock. , 1967, Research publications - Association for Research in Nervous and Mental Disease.