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10 - Toward an understanding of the function of sleep: New insights from mouse genetics

Published online by Cambridge University Press:  10 March 2010

By
Valter Tucci  and
Patrick M. Nolan
Edited by
Patrick McNamara ,
Robert A. Barton  and
Charles L. Nunn
Patrick McNamara
Affiliation:
Boston University
Robert A. Barton
Affiliation:
University of Durham
Charles L. Nunn
Affiliation:
Max Planck Institute for Evolutionary Anthropology
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Summary

Whether all species sleep or meet the common definition of sleep has recently been questioned (Siegel, 2008). In the majority of species that do sleep, however, the evolutionary conservation of DNA elements regulating sleep and its features highlights the physiological importance of this behavior. From an “adaptation” point of view, we would like to think of sleep as solving a problem, just as we do for traits such as eating, drinking, and so on. In such a perspective, the perpetuation of particular sleep genes would have occurred through improved fitness of the individuals with those genes. Clear scientific evidence on this matter, however, is still missing. Historically, the science of sleep has evolved from a key technological innovation: the development of electrophysiological instruments that allow the recording of changes in electrical activity in brain and muscles. Such a phenomenological approach has been successful in providing a practical framework for understanding “how” we sleep, but it has not contributed to solving the question of “why” we sleep.

The year 1953 was an important year for two important research fields: sleep and genetics. The discovery of rapid-eye-movement (REM) sleep at the University of Chicago, announced in Science (Aserinsky & Kleitman, 1953), laid the foundation for modern research on sleep. That same year, from the Cavendish laboratory in Cambridge, UK, Crick and Watson sent their proposal of a structural model of DNA to Nature (Watson & Crick, 1953b).

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Type
Chapter
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Evolution of Sleep
Phylogenetic and Functional Perspectives
 , pp. 218 - 237
Publisher: Cambridge University Press
Print publication year: 2009

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References

Akhtar, R. A., Reddy, A. B., Maywood, E. S., Clayton, J. D., King, V. M., Smith, A., et al. (2002). Circadian cycling of the mouse liver transcriptome, as revealed by cDNA microarray, is driven by the suprachiasmatic nucleus. Current Biology, 12(7), 540–550.CrossRefGoogle ScholarPubMed
Amici, R., Sanford, L. D., , Kearney K., McInerney, B., Ross, R. J., Horner, R. L., et al. (2004). A serotonergic (5-HT2) receptor mechanism in the laterodorsal tegmental nucleus participates in regulating the pattern of rapid-eye-movement sleep occurrence in the rat. Brain Research, 996(1), 9–18.CrossRefGoogle ScholarPubMed
Anokhin, A., Steinlein, O., Fischer, C., Mao, Y., Vogt, P., Schalt, E., et al. (1992). A genetic study of the human low-voltage electroencephalogram. Human Genetics, 90(1–2), 99–112.CrossRefGoogle ScholarPubMed
Aserinsky, E., & Kleitman, N. (1953). Regularly occurring periods of eye motility, and concomitant phenomena, during sleep. Science, 118(3062), 273–274.CrossRefGoogle ScholarPubMed
Bacon, Y., Ooi, A., Kerr, S., Shaw-Andrews, L., Winchester, L., Breeds, S., et al. (2004). Screening for novel ENU-induced rhythm, entrainment, and activity mutants. Genes, Brain, and Behavior, 3, 196–205.CrossRefGoogle ScholarPubMed
Bates, G. P., Harper, P. S., & Jones, L. (2002). Huntington's disease. Oxford, UK: Oxford University Press.Google Scholar
Benington, J. H., & Heller, H. C. (1995). Restoration of brain energy metabolism as the function of sleep. Progress in Neurobiology, 45(4), 347–360.CrossRefGoogle ScholarPubMed
Berridge, C. W. (2007). Noradrenergic modulation of arousal. Brain Research Reviews, 58(1), 1–17.CrossRefGoogle ScholarPubMed
Berridge, C. W., Isaac, S. O., & España, R. A. (2003). Additive wake-promoting actions of medial basal forebrain noradrenergic alpha1- and beta-receptor stimulation. Behavioral Neuroscience, 117(2), 350–359.CrossRefGoogle ScholarPubMed
Borbély, A. A. (1982). A two-process model of sleep regulation. Human Neurobiology, 1, 195–204.Google ScholarPubMed
Cirelli, C. (2002). How sleep deprivation affects gene expression in the brain: A review of recent findings. Journal of Applied Physiology, 92(1), 394–400.CrossRefGoogle ScholarPubMed
Cirelli, C., Gutierrez, C. M., & Tononi, G. (2004). Extensive and divergent effects of sleep and wakefulness on brain gene expression. Neuron, 41(1), 35–43.CrossRefGoogle ScholarPubMed
Cirelli, C., & Tononi, G. (1998). Differences in gene expression between sleep and waking as revealed by mRNA differential display. Brain Research, Molecular Brain Research, 56(1–2), 293–305.CrossRefGoogle ScholarPubMed
Clayton-Smith, J., & Laan, L. (2003). Angelman syndrome: A review of the clinical and genetic aspects. Journal of Medical Genetics, 40(2), 87–95.CrossRefGoogle ScholarPubMed
Colas, D., Wagstaff, J., Fort, P., Salvert, D., & Sarda, N. (2005). Sleep disturbances in Ube3a maternal deficient mice modeling Angelman syndrome. Neurobiology of Disease, 20, 471–478.CrossRefGoogle ScholarPubMed
Constancia, M., Kelsey, G., & Reik, W. (2004). Resourceful imprinting. Nature, 432(7013), 53–57.CrossRefGoogle ScholarPubMed
Daan, S., Beersma, D. G., & Borbély, A. A. (1984). Timing of human sleep: Recovery process gated by a circadian pacemaker. American Journal of Physiology, 246(2 Pt. 2), R161–R183.Google ScholarPubMed
Dudley, C. A., Erbel-Sieler, C., Estill, S. J., Reick, M., Franken, P., Pitts, S., et al. (2003). Altered patterns of sleep and behavioral adaptability in NPAS2-deficient mice. Science, 301(5631), 379–383.CrossRefGoogle ScholarPubMed
Etter, P. D., & Ramaswami, M. (2002). The ups and downs of daily life: Profiling circadian gene expression in Drosophila. Bioessays, 24(6), 494–498.CrossRefGoogle ScholarPubMed
Franken, P., Chollet, D., & Tafti, M. (2001). The homeostatic regulation of sleep need is under genetic control. Journal of Neuroscience, 21, 2610–2621.CrossRefGoogle ScholarPubMed
Franken, P., Lopez-Molina, L., Marcacci, L., Schibler, U., & Tafti, M. (2000). The transcription factor DBP affects circadian sleep consolidation and rhythmic EEG activity. Journal of Neuroscience, 20(2), 617–625.CrossRefGoogle ScholarPubMed
Franken, P., Malafosse, A., & Tafti, M. (1998). Genetic variation in EEG activity during sleep in inbred mice. American Journal of Physiology, 275(4 Pt. 2), R1127–R1137.Google ScholarPubMed
Franken, P., Malafosse, A., & Tafti, M. (1999). Genetic determinants of sleep regulation in inbred mice. Sleep, 22(2), 155–169.Google ScholarPubMed
Franken, P., Thomason, R., Heller, H. C., & O'Hara, B. F. (2007). A non-circadian role for clock-genes in sleep homeostasis: A strain comparison. BMC Neuroscience, 8, 87.CrossRefGoogle ScholarPubMed
Franken, P., Tobler, I., & Borbély, A. A. (1993). Effects of 12-h sleep deprivation and of 12-h cold exposure on sleep regulation and cortical temperature in the rat. Physiology and Behavior, 54(5), 885–894.CrossRefGoogle ScholarPubMed
Friedmann, J. K. (1974). A diallel analysis of the genetic underpinning of mouse sleep. Physiology and Behavior, 12, 169–175.CrossRefGoogle Scholar
Godinho, S. I. H., Maywood, E. S., Shaw, L., Tucci, V., Barnard, A. R., Busino, L., et al. (2007). The after-hours mutant mouse reveals a role for Fbxl3 in determining mammalian circadian period. Science, 316(5826), 897–900.CrossRefGoogle ScholarPubMed
Haig, D., & Westoby, M. (2006). An earlier formulation of the genetic conflict hypothesis of genomic imprinting. Nature Genetics, 38(3), 271.CrossRefGoogle ScholarPubMed
Hertz, G., Cataletto, M., Feinsilver, S. H., & Angulo, M. (1993). Sleep and breathing patterns in patients with Prader Willi syndrome (PWS): Effects of age and gender. Sleep, 16(4), 366–371.CrossRefGoogle ScholarPubMed
Hess, W. R. (1965). Sleep as a phenomenon of the integral organism. In Akert, K., Bally, C., & Schade, J. P. (Eds.), Progress in brain research. Sleep mechanisms (pp. 3–8). Amsterdam: Elsevier.CrossRefGoogle Scholar
Hobson, J. A. (2005). Sleep is of the brain, by the brain, and for the brain. Nature, 437(7063), 1254–1256.CrossRefGoogle Scholar
Hofstetter, J. R., Svihla-Jones, D. A., & Mayeda, A. R. (2007). A QTL on mouse chromosome 12 for the genetic variance in free-running circadian period between inbred strains of mice. Journal of Circadian Rhythms, 5, 7.CrossRefGoogle ScholarPubMed
Hofstetter, J. R., Trofatter, J. A., Kernek, K. L., Nurnberger, J. I., & Mayeda, A. R. (2003). New quantitative trait loci for the genetic variance in circadian period of locomotor activity between inbred strains of mice. Journal of Biological Rhythms, 18(6), 450–462.CrossRefGoogle ScholarPubMed
Hu, W. P., Li, J. D., Zhang, C., Boehmer, L., Siegel, J. M., & Zhou, Q. Y. (2007). Altered circadian and homeostatic sleep regulation in prokineticin 2-deficient mice. Sleep, 30(3), 247–256.Google ScholarPubMed
Huber, R., Deboer, T., & Tobler, I. (2000). Effects of sleep deprivation on sleep and sleep EEG in three mouse strains: Empirical data and simulations. Brain Research, 857(1–2), 8–19.CrossRefGoogle ScholarPubMed
Kapfhamer, D., Valladares, O., Sun, Y., Nolan, P. M., Rux, J. J., Arnold, S. E., et al. (2002). Mutations in Rab3a alter circadian period and homeostatic response to sleep loss in the mouse. Nature Genetics, 32(2), 290–295.CrossRefGoogle ScholarPubMed
Kassubek, J., Juengling, F. D., Kioschies, T., Henkel, K., Karitzky, J., Kramer, B., et al. (2004). Topography of cerebral atrophy in early Huntington's disease: A voxel-based morphometric MRI study. Journal of Neurology, Neurosurgery, and Psychiatry, 75(2), 213–220.Google ScholarPubMed
Kimura, M., & Winkelmann, J. (2007). Genetics of sleep and sleep disorders. Cellular and Molecular Life Sciences, 64(10), 1216–1226.CrossRefGoogle ScholarPubMed
Kobayashi, S., Kohda, T., Miyoshi, N., Kuroiwa, Y., Aisaka, K., Tsutsumi, O., et al. (1997). Human PEG1/MEST, an imprinted gene on chromosome 7. Human Molecular Genetics, 6(5), 781–786.CrossRefGoogle ScholarPubMed
Kopp, C., Albrecht, U., Zheng, B., & Tobler, I. (2002). Homeostatic sleep regulation is preserved in mPer1 and mPer2 mutant mice. European Journal of Neuroscience, 16(6), 1099–1106.CrossRefGoogle ScholarPubMed
Kozlov, S. V., Bogenpohl, J. W., Howell, M. P., Wevrick, R., Panda, S., Hogenesch, J. B., et al. (2007). The imprinted gene Magel2 regulates normal circadian output. Nature Genetics, 39(10), 1266–1272.CrossRefGoogle ScholarPubMed
Lalande, M., Minassian, B. A., DeLorey, T. M., & Olsen, R. W. (1999). Parental imprinting and Angelman syndrome. Advances in Neurology, 79, 421–429.Google ScholarPubMed
Laposky, A., Easton, A., Dugovic, C., Walisser, J., Bradfield, C., & Turek, F. (2005). Deletion of the mammalian circadian clock gene BMAL1/Mop3 alters baseline sleep architecture and the response to sleep deprivation. Sleep, 28(4), 395–409.CrossRefGoogle ScholarPubMed
Liljelund, P., Handforth, A., Homanies, G., & Olsen, R. (2005). GABAA receptor beta3 subunit gene-deficient heterozygous mice show parent-of-origin and gender-related differences in beta3 subunit levels, EEG, and behavior. Developmental Brain Research, 157(2), 150–161.CrossRefGoogle ScholarPubMed
Linkowski, P., Kerkhofs, M., Hauspie, R., & Mendlewicz, J. (1991). Genetic determinants of EEG sleep: A study in twins living apart. Electroencephalography and Clinical Neurophysiology, 79(2), 114–118.CrossRefGoogle ScholarPubMed
Loewenstein, R. J., Weingartner, H., Gillin, J. C., Kaye, W., Ebert, M., & Mendelson, W. B. (1982). Disturbances of sleep and cognitive functioning in patients with dementia. Neurobiology of Aging, 3(4), 371–377.CrossRefGoogle ScholarPubMed
Mackiewicz, M., Paigen, B., Naidoo, N., & Pack, I. A. (2008). Analysis of the QTL for sleep homeostasis in mice: Homer1a is a likely candidate. Physiological Genomics, 33(1), 91–99.CrossRefGoogle ScholarPubMed
Mackiewicz, M., Shockley, K. R., Romer, M. A., Galante, R. J., Zimmerman, J. E., Naidoo, N., et al. (2007). Macromolecule biosynthesis: A key function of sleep. Physiological Genomics, 31(3), 441–457.CrossRefGoogle ScholarPubMed
Maret, S., Dorsaz, S., Gurcel, L., Pradervand, S., Petit, B., Pfister, C., et al. (2007). Homer1a is a core brain molecular correlate of sleep loss. Proceedings of the National Academy of Sciences of the United States of America, 104(50), 20090–20095.CrossRefGoogle ScholarPubMed
McCarley, R. W., & Hobson, J. A. (1975). Neuronal excitability modulation over the sleep cycle: A structural and mathematical model. Science, 189(4196), 58–60.CrossRefGoogle ScholarPubMed
McNamara, P. (2004). Genomic imprinting and neurodevelopmental disorders of sleep. Sleep and Hypnosis, 6(2), 100–108.Google Scholar
Montplaisir, J., Petit, D., Lorrain, D., Gauthier, S., & Nielsen, T. (1995). Sleep in Alzheimer's disease: Further considerations on the role of brainstem and forebrain cholinergic populations in sleep-wake mechanisms. Sleep, 18(3), 145–148.CrossRefGoogle ScholarPubMed
Morairty, S. R., Hedley, L., Flores, J., Martin, R., & Kilduff, T. S. (2008). Selective 5HT2A and 5HT6 receptor antagonists promote sleep in rats. Sleep, 31(1), 34–44.CrossRefGoogle ScholarPubMed
Morton, A. J., Wood, N. I., Hastings, M. H., Barker, R. A., & Maywood, E. S. (2005). Disintegration of the sleep-wake cycle and circadian timing in Huntington's disease. Journal of Neuroscience, 25(1), 157–163.CrossRefGoogle ScholarPubMed
Naylor, E., Bergmann, B. M., Krauski, K., Zee, P. C., Takahashi, J. S., Hotz Vitaterna, M., et al. (2000). The circadian clock mutation alters sleep homeostasis in the mouse. Journal of Neuroscience, 20(21), 8138–8143.CrossRefGoogle ScholarPubMed
Nishino, S. (2007). The hypothalamic peptidergic system, hypocretin/orexin and vigilance control. Neuropeptides, 41(3), 117–133.CrossRefGoogle ScholarPubMed
Nolan, P. M., Peters, J., Strivens, M., Rogers, D., Hagen, J., Spurr, N., et al. (2000). A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse. Nature Genetics, 25(4), 440–443.CrossRefGoogle ScholarPubMed
O'Hara, B. F., Ding, J., Bernat, R. L., & Franken, P. (2007). Genomic and proteomic approaches towards an understanding of sleep. CNS and Neurological Disorders – Drug Targets, 6(1), 71–81.CrossRefGoogle Scholar
Pack, A. I., Galante, R. J., Maislin, G., Cater, J., Metaxas, D., Lu, S., et al. (2007). Novel method for high-throughput phenotyping of sleep in mice. Physiological Genomics, 28(2), 232–238.CrossRefGoogle ScholarPubMed
Panda, S., Antoch, M. P., Miller, B. H., Su, A. I., Schook, A. B., Straume, M., et al. (2002). Coordinated transcription of key pathways in the mouse by the circadian clock. Cell, 109(3), 307–320.CrossRefGoogle ScholarPubMed
Panda, S., Hogenesch, J. B., & Kay, S. A. (2002). Circadian rhythms from flies to human. Nature, 417(6886), 329–335.CrossRefGoogle ScholarPubMed
Peters, J., & Williamson, C. M. (2007). Control of imprinting at the gnas cluster. Epigenetics, 2(4), 207–213.CrossRefGoogle ScholarPubMed
Plagge, A., Gordon, E., Dean, W., Boiani, R., Cinti, S., Peters, J., et al. (2004). The imprinted signaling protein XL alpha s is required for postnatal adaptation to feeding. Nature Genetics, 36(8), 818–826.CrossRefGoogle Scholar
Plagge, A., Isles, A. R., Gordon, E., Humby, T., Dean, W., Gritsch, S., et al. (2005). Imprinted Nesp55 influences behavioral reactivity to novel environments. Molecular and Cellular Biology, 25(8), 3019–3026.CrossRefGoogle ScholarPubMed
Pompeiano, M., Cirelli, C., & Tononi, G. (1994). Immediate-early genes in spontaneous wakefulness and sleep: Expression of c-fos and NGFI-A mRNA and protein. Journal of Sleep Research, 3(2), 80–96.CrossRefGoogle ScholarPubMed
Porkka-Heiskanen, T., Strecker, R. E., & McCarley, R. W. (2000). Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep: An in vivo microdialysis study. Neuroscience, 99(3), 507–517.CrossRefGoogle Scholar
Prinz, P. N., Vitaliano, P. P., Vitiello, M. V., Bokan, J., Raskind, M., Peskind, E., et al. (1982). Sleep, EEG and mental function changes in senile dementia of the Alzheimer's type. Neurobiology of Aging, 3(4), 361–370.CrossRefGoogle ScholarPubMed
Sanford, L. D., Yang, L., & Tang, X. (2003). Influence of contextual fear on sleep in mice: A strain comparison. Sleep, 26(5), 527–540.CrossRefGoogle ScholarPubMed
Shiromani, P. J., Xu, M., Winston, E. M., Shiromani, S. N., Gerashchenko, D., & Weaver, D. R. (2004). Sleep rhythmicity and homeostasis in mice with targeted disruption of mPeriod genes. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 287(1), R47–R57.Google ScholarPubMed
Siegel, J. M. (2008). Do all animals sleep?Trends in Neurosciences, 31, 2008–2213.CrossRefGoogle ScholarPubMed
Silvestri, R., Raffaele, M., Domenico, P., Tisano, A., Mento, G., Casella, C., et al. (1995). Sleep features in Tourette's syndrome, neuroacanthocytosis, and Huntington's chorea. Neurophysiologie Clininique, 25(2), 66–77.CrossRefGoogle ScholarPubMed
Steriade, M., McCormick, D. A., & Sejnowski, T. J. (1993). Thalamocortical oscillations in the sleeping and aroused brain. Science, 262(5134), 679–685.CrossRefGoogle ScholarPubMed
Tafti, M. (2007). Quantitative genetics of sleep in inbred mice. Dialogues in Clinical Neuroscience, 9(3), 273–278.Google ScholarPubMed
Tafti, M., Chollet, D., Valatx, J.-L., & Franken, P. (1999). Quantitative trait loci approach to the genetics of sleep in recombinant inbred mice. Journal of Sleep Research, 8(S1), 37–43.CrossRefGoogle ScholarPubMed
Tafti, M., Franken, P., Kitahama, K., Malafosse, A., Jouvet, M., & Valatx, J.-L. (1997). Localization of candidate genomic regions influencing paradoxical sleep in mice. NeuroReport, 8(17), 3755–3758.CrossRefGoogle ScholarPubMed
Tafti, M., Maret, S., & Dauvilliers, Y. (2005). Genes for normal sleep and sleep disorders. Annals of Medicine, 37(8), 580–589.CrossRefGoogle ScholarPubMed
Tang, X., & Sanford, L. D. (2002). Telemetric recording of sleep and home cage activity in mice. Sleep, 25(6), 691–699.CrossRefGoogle ScholarPubMed
Terao, A., Wisor, J. P., Peyron, C., Apte-Deshpande, A., Wurts, S. W., Edgar, D. M., et al. (2006). Gene expression in the rat brain during sleep deprivation and recovery sleep: An Affymetrix GeneChip study. Neuroscience, 137(2), 593–605.CrossRefGoogle ScholarPubMed
Tobler, I., & Borbély, A. A. (1990). The effect of 3-h and 6-h sleep deprivation on sleep and EEG spectra of the rat. Behavioural Brain Research, 36(1–2), 73–78.CrossRefGoogle ScholarPubMed
Tucci, V., Achilli, F., Blanco, G., Lad, H. V., Wells, S., Godinho, S., et al. (2007). Reaching and grasping phenotypes in the mouse (Mus musculus): A characterization of inbred strains and mutant lines. Neuroscience, 147(3), 573–582.CrossRefGoogle ScholarPubMed
Valatx, J. L., Bugat, R., & Jouvet, M. (1972). Genetic studies of sleep in mice. Nature, 238(5361), 226–227.CrossRefGoogle ScholarPubMed
Vela-Bueno, A., Kales, A., Soldatos, C. R., Dobladez-Blanco, B., Campos-Castello, J., Espino-Hurtado, P., et al. (1984). Sleep in the Prader-Willi syndrome: Clinical and polygraphic findings. Archives of Neurology, 41(3), 294–296.CrossRefGoogle ScholarPubMed
Verducci, J. S., Melfi, V. F., Lin, S., Wang, Z., Roy, S., & Sen, C. K. (2006). Microarray analysis of gene expression: Considerations in data mining and statistical treatment. Physiological Genomics, 25(3), 355–363.CrossRefGoogle ScholarPubMed
Vertes, R. P., & Kocsis, B. (1997). Brainstem-diencephalo-septohippocampal systems controlling the theta rhythm of the hippocampus. Neuroscience, 81(4), 893–926.Google ScholarPubMed
Vgontzas, A. N., Kales, A., Seip, J., Mascari, M. J., Bixler, E. O., Myers, D. O., et al. (1996). Relationship of sleep abnormalities to patient genotypes in Prader-Willi syndrome. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 67(5), 478–482.3.0.CO;2-G>CrossRefGoogle ScholarPubMed
Vinogradova, O. S. (1995). Expression, control, and probable functional significance of the neuronal theta-rhythm. Progress in Neurobiology, 45(6), 523–583.CrossRefGoogle ScholarPubMed
Walker, M. P., Brakefield, T., Hobson, J. A., & Stickgold, R. (2003). Dissociable stages of human memory consolidation and reconsolidation. Nature, 425(6958), 616–620.CrossRefGoogle ScholarPubMed
Watson, J. D., & Crick, F. H. C. (1953a). Genetical implications of the structure of deoxyribonucleic acid. Nature, 171(4361), 964–967.CrossRefGoogle ScholarPubMed
Watson, J. D., & Crick, F. H. C. (1953b). Molecular structure of nucleic acids; A structure for deoxyribose nucleic acid. Nature, 171(4356), 737–738.CrossRefGoogle ScholarPubMed
Wisor, J. P., O'Hara, B. F., Terao, A., Selby, C. P., Kilduff, T. S., Sancar, A., et al. (2002). A role for cryptochromes in sleep regulation. BMC Neuroscience, 3, 20.CrossRefGoogle ScholarPubMed
Zhdanova, I. V., Wurtman, R. J., & Wagstadd, J. (1999). Effects of a low dose of melatonin on sleep in children with Angelman syndrome. Journal of Pediatric Endocrinology and Metabolism, 12(1), 57–67.CrossRefGoogle ScholarPubMed

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