Loss of Imprinting Differentially Affects REM/NREM Sleep and Cognition in Mice
It has been suggested that imprinted genes are important in the regulation of sleep. However, the fundamental question of whether genomic imprinting has a role in sleep has remained elusive up to now. In this work we show that REM and NREM sleep states are differentially modulated by the maternally expressed imprinted gene Gnas. In particular, in mice with loss of imprinting of Gnas, NREM and complex cognitive processes are enhanced while REM and REM–linked behaviors are inhibited. This is the first demonstration that a specific overexpression of an imprinted gene affects sleep states and related complex behavioral traits. Furthermore, in parallel to the Gnas overexpression, we have observed an overexpression of Ucp1 in interscapular brown adipose tissue (BAT) and a significant increase in thermoregulation that may account for the REM/NREM sleep phenotypes. We conclude that there must be significant evolutionary advantages in the monoallelic expression of Gnas for REM sleep and for the consolidation of REM–dependent memories. Conversely, biallelic expression of Gnas reinforces slow wave activity in NREM sleep, and this results in a reduction of uncertainty in temporal decision-making processes.
Vyšlo v časopise:
Loss of Imprinting Differentially Affects REM/NREM Sleep and Cognition in Mice. PLoS Genet 8(5): e32767. doi:10.1371/journal.pgen.1002706
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002706
Souhrn
It has been suggested that imprinted genes are important in the regulation of sleep. However, the fundamental question of whether genomic imprinting has a role in sleep has remained elusive up to now. In this work we show that REM and NREM sleep states are differentially modulated by the maternally expressed imprinted gene Gnas. In particular, in mice with loss of imprinting of Gnas, NREM and complex cognitive processes are enhanced while REM and REM–linked behaviors are inhibited. This is the first demonstration that a specific overexpression of an imprinted gene affects sleep states and related complex behavioral traits. Furthermore, in parallel to the Gnas overexpression, we have observed an overexpression of Ucp1 in interscapular brown adipose tissue (BAT) and a significant increase in thermoregulation that may account for the REM/NREM sleep phenotypes. We conclude that there must be significant evolutionary advantages in the monoallelic expression of Gnas for REM sleep and for the consolidation of REM–dependent memories. Conversely, biallelic expression of Gnas reinforces slow wave activity in NREM sleep, and this results in a reduction of uncertainty in temporal decision-making processes.
Zdroje
1. CirelliC 2009 The genetic and molecular regulation of sleep: from fruit flies to humans. Nat Rev Neurosci 10 549 560
2. SehgalAMignotE 2011 Genetics of sleep and sleep disorders. Cell 146 194 207
3. McNamaraP 2004 Genomic imprinting and neurodevelopmental disorders of sleep. Sleep and Hypnosis 6 82 90
4. McNamaraPDowdallJAuerbachS 2002 REM sleep, early experience, and the development of reproductive strategies. Human Nature 13 405 435
5. Vela-BuenoAKalesASoldatosCRDobladez-BlancoBCampos-CastelloJ 1984 Sleep in the Prader-Willi syndrome. Clinical and polygraphic findings. Arch Neurol 41 294 296
6. HertzGCatalettoMFeinsilverSHAnguloM 1993 Sleep and breathing patterns in patients with Prader Willi syndrome (PWS): effects of age and gender. Sleep 16 366 371
7. VgontzasANBixlerEOKalesACenturioneARoganPK 1996 Daytime sleepiness and REM abnormalities in Prader-Willi syndrome: evidence of generalized hypoarousal. Int J Neurosci 87 127 139
8. VgontzasANKalesASeipJMascariMJBixlerEO 1996 Relationship of sleep abnormalities to patient genotypes in Prader-Willi syndrome. Am J Med Genet 67 478 482
9. ColasDWagstaffJFortPSalvertDSardaN 2005 Sleep disturbances in Ube3a maternal-deficient mice modeling Angelman syndrome. Neurobiol Dis 20 471 478
10. AmiciRSanfordLDKearneyKMcInerneyBRossRJ 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 Res 996 9 18
11. KatoMVShimizuTNagayoshiMKanekoASasakiMS 1996 Genomic imprinting of the human serotonin-receptor (HTR2) gene involved in development of retinoblastoma. Am J Hum Genet 59 1084 1090
12. KatoMVIkawaYHayashizakiYShibataH 1998 Paternal imprinting of mouse serotonin receptor 2A gene Htr2 in embryonic eye: a conserved imprinting regulation on the RB/Rb locus. Genomics 47 146 148
13. DiekelmannSBornJ 2010 The memory function of sleep. Nat Rev Neurosci 11 114 126
14. ChenMNemechekNMMemaEWangJWeinsteinLS 2011 Effects of deficiency of the G protein Gsalpha on energy and glucose homeostasis. Eur J Pharmacol 660 119 124
15. ChenMChenHNguyenAGuptaDWangJ 2010 G(s)alpha deficiency in adipose tissue leads to a lean phenotype with divergent effects on cold tolerance and diet-induced thermogenesis. Cell Metab 11 320 330
16. WilliamsonCMBallSTNottinghamWTSkinnerJAPlaggeA 2004 A cis-acting control region is required exclusively for the tissue-specific imprinting of Gnas. Nat Genet 36 894 899
17. JakusPBSandorAJanakyTFarkasV 2008 Cooperation between BAT and WAT of rats in thermogenesis in response to cold, and the mechanism of glycogen accumulation in BAT during reacclimation. J Lipid Res 49 332 339
18. CannonBNedergaardJ 2004 Brown adipose tissue: function and physiological significance. Physiol Rev 84 277 359
19. SanfordLDYangLWellmanLLLiuXTangX 2010 Differential effects of controllable and uncontrollable footshock stress on sleep in mice. Sleep 33 621 630
20. CaiDJShumanTHarrisonEMSageJRAnagnostarasSG 2009 Sleep deprivation and Pavlovian fear conditioning. Learn Mem 16 595 599
21. CaiDJMednickSAHarrisonEMKanadyJCMednickSC 2009 REM, not incubation, improves creativity by priming associative networks. Proc Natl Acad Sci U S A 106 10130 10134
22. BalciFFreestoneDGallistelCR 2009 Risk assessment in man and mouse. Proc Natl Acad Sci U S A 106 2459 2463
23. BalciFSimenPNiyogiRSaxeAHughesJA 2011 Acquisition of decision making criteria: reward rate ultimately beats accuracy. Atten Percept Psychophys 73 640 657
24. KrauchiKDeboerT 2010 The interrelationship between sleep regulation and thermoregulation. Front Biosci 15 604 625
25. ValatxJLRousselBCureM 1973 [Sleep and cerebral temperature in rat during chronic heat exposure]. Brain Res 55 107 122
26. AmiciRCerriMOcampo-GarcesABaracchiFDenticoD 2008 Cold exposure and sleep in the rat: REM sleep homeostasis and body size. Sleep 31 708 715
27. MorairtySRSzymusiakRThomsonDMcGintyDJ 1993 Selective increases in non-rapid eye movement sleep following whole body heating in rats. Brain Res 617 10 16
28. GaoBOFrankenPToblerIBorbelyAA 1995 Effect of elevated ambient temperature on sleep, EEG spectra, and brain temperature in the rat. Am J Physiol 268 R1365 1373
29. ObalFJrAlfoldiPRubicsekG 1995 Promotion of sleep by heat in young rats. Pflugers Arch 430 729 738
30. PuigserverPSpiegelmanBM 2003 Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 24 78 90
31. HendricksJCWilliamsJAPanckeriKKirkDTelloM 2001 A non-circadian role for cAMP signaling and CREB activity in Drosophila rest homeostasis. Nat Neurosci 4 1108 1115
32. GravesLAHellmanKVeaseySBlendyJAPackAI 2003 Genetic evidence for a role of CREB in sustained cortical arousal. J Neurophysiol 90 1152 1159
33. JoinerWJCrockerAWhiteBHSehgalA 2006 Sleep in Drosophila is regulated by adult mushroom bodies. Nature 441 757 760
34. AnagnostarasSGGaleGDFanselowMS 2001 Hippocampus and contextual fear conditioning: recent controversies and advances. Hippocampus 11 8 17
35. GarciaJAZhangDEstillSJMichnoffCRutterJ 2000 Impaired cued and contextual memory in NPAS2-deficient mice. Science 288 2226 2230
36. ChenMWangJDickersonKEKelleherJXieT 2009 Central nervous system imprinting of the G protein G(s)alpha and its role in metabolic regulation. Cell Metab 9 548 555
37. BuijsRMvan EdenCGGoncharukVDKalsbeekA 2003 The biological clock tunes the organs of the body: timing by hormones and the autonomic nervous system. J Endocrinol 177 17 26
38. BalciFPapachristosEBGallistelCRBrunnerDGibsonJ 2008 Interval timing in genetically modified mice: a simple paradigm. Genes Brain Behav 7 373 384
39. PlaggeAGordonEDeanWBoianiRCintiS 2004 The imprinted signaling protein XL alpha s is required for postnatal adaptation to feeding. Nat Genet 36 818 826
40. BerridgeCWIsaacSOEspanaRA 2003 Additive wake-promoting actions of medial basal forebrain noradrenergic alpha1- and beta-receptor stimulation. Behav Neurosci 117 350 359
41. BerridgeCW 2008 Noradrenergic modulation of arousal. Brain Res Rev 58 1 17
42. WilliamsonCMTurnerMDBallSTNottinghamWTGlenisterP 2006 Identification of an imprinting control region affecting the expression of all transcripts in the Gnas cluster. Nat Genet 38 350 355
43. WinnVDHaimov-KochmanRPaquetACYangYJMadhusudhanMS 2007 Gene expression profiling of the human maternal-fetal interface reveals dramatic changes between midgestation and term. Endocrinology 148 1059 1079
44. PossentiRal.E 2011 Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of VGF-derived peptide TLQP-21. Biochem J In Press
45. FrankenPMalafosseATaftiM 1998 Genetic variation in EEG activity during sleep in inbred mice. Am J Physiol 275 R1127 1137
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2012 Číslo 5
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- Inactivation of a Novel FGF23 Regulator, FAM20C, Leads to Hypophosphatemic Rickets in Mice
- Genome-Wide Association of Pericardial Fat Identifies a Unique Locus for Ectopic Fat
- Slowing Replication in Preparation for Reduction
- Deletion of PTH Rescues Skeletal Abnormalities and High Osteopontin Levels in Mice