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Disease relevance of Wakefulness


Psychiatry related information on Wakefulness

  • Targeted disruption of the orexin gene in mice produces a syndrome remarkably similar to human and canine narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and other pathological manifestations of the intrusion of REM sleep-related features into wakefulness [6].
  • The results indicate that (1) iontophoretic application of the GABA antagonist bicuculline reversed the typical suppression of neuronal activity seen during slow wave sleep, but had no effect on maintained activity during wakefulness [7].
  • Orexin-containing neurons regulate wakefulness, and loss of orexin produces narcolepsy [8].
  • The present experiments in 10 adult men were designed to examine whether or not REM sleep inhibits adrenocortical activity and if short periods of wakefulness increase nocturnal cortisol release [9].
  • In patients and controls an inverse relationship between plasma AVP concentrations and motor activity during wakefulness was found [10].

High impact information on Wakefulness

  • To eat or to sleep? Orexin in the regulation of feeding and wakefulness [6].
  • As most of these cells are also inhibited by serotonin but unaffected by histamine, their overall inhibition by transmitters of wakefulness is in agreement with their relative inactivity during waking with respect to sleep [11].
  • We also show that these neurons are inhibited by noradrenaline and acetylcholine, both of which are transmitters of wakefulness [11].
  • Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness [12].
  • Early morning insomnia, a significant increase in wakefulness during the final hours of drug nights, occurred after 1 or 2 weeks of nightly administration of benzodiazepine hypnotics with short elimination half-lives, when tolerance had begun to develop [13].

Chemical compound and disease context of Wakefulness


Biological context of Wakefulness


Anatomical context of Wakefulness


Gene context of Wakefulness

  • Both OX2R(-/-) and orexin(-/-) mice are similarly affected with behaviorally abnormal attacks of non-REM sleep ("sleep attacks") and show similar degrees of disrupted wakefulness [31].
  • Here, we report that a neuropeptide, neuropeptide S (NPS), potently modulates wakefulness and could also regulate anxiety [32].
  • Both the top and end hormones of the hypothalamic-pituitary-adrenal axis, i.e. CRH and glucocorticoids, stimulate arousal/wakefulness and inhibit slow wave (deep) sleep in experimental animals and man [33].
  • CRH induced an increase in EEG activity in the sigma frequency range, both when it was administered during wakefulness and SWS, while this effect was reduced by pre-treatment with GHRH [34].
  • Characterization of ergot and non-ergot serotonin antagonists by prolactin and growth hormone profiles during wakefulness and sleep [35].

Analytical, diagnostic and therapeutic context of Wakefulness


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  3. Sleep and quantitative EEG in patients with progressive supranuclear palsy. Montplaisir, J., Petit, D., Décary, A., Masson, H., Bédard, M.A., Panisset, M., Rémillard, G., Gauthier, S. Neurology (1997) [Pubmed]
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  7. Neurochemical afferents controlling the activity of serotonergic neurons in the dorsal raphe nucleus: microiontophoretic studies in the awake cat. Levine, E.S., Jacobs, B.L. J. Neurosci. (1992) [Pubmed]
  8. Wakefulness: an eye-opening perspective on orexin neurons. Scammell, T.E. Curr. Biol. (2001) [Pubmed]
  9. Influences of partial REM sleep deprivation and awakenings on nocturnal cortisol release. Born, J., Schenk, U., Späth-Schwalbe, E., Fehm, H.L. Biol. Psychiatry (1988) [Pubmed]
  10. Plasma arginine vasopressin and motor activity in major depression. van Londen, L., Kerkhof, G.A., van den Berg, F., Goekoop, J.G., Zwinderman, K.H., Frankhuijzen-Sierevogel, A.C., Wiegant, V.M., de Wied, D. Biol. Psychiatry (1998) [Pubmed]
  11. Identification of sleep-promoting neurons in vitro. Gallopin, T., Fort, P., Eggermann, E., Cauli, B., Luppi, P.H., Rossier, J., Audinat, E., Mühlethaler, M., Serafin, M. Nature (2000) [Pubmed]
  12. Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness. Porkka-Heiskanen, T., Strecker, R.E., Thakkar, M., Bjorkum, A.A., Greene, R.W., McCarley, R.W. Science (1997) [Pubmed]
  13. Early morning insomnia with rapidly eliminated benzodiazepines. Kales, A., Soldatos, C.R., Bixler, E.O., Kales, J.D. Science (1983) [Pubmed]
  14. Nocturnal oxygen desaturation in patients with sickle cell anemia. Scharf, M.B., Lobel, J.S., Caldwell, E., Cameron, B.F., Kramer, M., De Marchis, J., Paine, C. JAMA (1983) [Pubmed]
  15. Progesterone administration and progressive sleep apneas. Strohl, K.P., Hensley, M.J., Saunders, N.A., Scharf, S.M., Brown, R., Ingram, R.H. JAMA (1981) [Pubmed]
  16. Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Huang, Z.L., Qu, W.M., Eguchi, N., Chen, J.F., Schwarzschild, M.A., Fredholm, B.B., Urade, Y., Hayaishi, O. Nat. Neurosci. (2005) [Pubmed]
  17. Circadian and sleep-related endocrine rhythms in schizophrenia. Van Cauter, E., Linkowski, P., Kerkhofs, M., Hubain, P., L'Hermite-Balériaux, M., Leclercq, R., Brasseur, M., Copinschi, G., Mendlewicz, J. Arch. Gen. Psychiatry (1991) [Pubmed]
  18. Potential brain neuronal targets for amphetamine-, methylphenidate-, and modafinil-induced wakefulness, evidenced by c-fos immunocytochemistry in the cat. Lin, J.S., Hou, Y., Jouvet, M. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  19. Prolonged wakefulness induces experience-dependent synaptic plasticity in mouse hypocretin/orexin neurons. Rao, Y., Liu, Z.W., Borok, E., Rabenstein, R.L., Shanabrough, M., Lu, M., Picciotto, M.R., Horvath, T.L., Gao, X.B. J. Clin. Invest. (2007) [Pubmed]
  20. Influence of wakefulness on pharyngeal airway muscle activity. Lo, Y.L., Jordan, A.S., Malhotra, A., Wellman, A., Heinzer, R.A., Eikermann, M., Schory, K., Dover, L., White, D.P. Thorax (2007) [Pubmed]
  21. Normal human sleep: regional cerebral hemodynamics. Sakai, F., Meyer, J.S., Karacan, I., Derman, S., Yamamoto, M. Ann. Neurol. (1980) [Pubmed]
  22. State-dependent hypotonia in posterior cricoarytenoid muscles of the larynx caused by cholinoceptive reticular mechanisms. Lydic, R., Baghdoyan, H.A., Zwillich, C.W. FASEB J. (1989) [Pubmed]
  23. Diazepam suppresses sleep apneas in rats. Carley, D.W., Trbovic, S.M., Radulovacki, M. Am. J. Respir. Crit. Care Med. (1998) [Pubmed]
  24. Circadian rhythms in sleep and wakefulness and in salivary melatonin and cortisol concentrations in mothers of term and preterm infants. McMillen, I.C., Mulvogue, H.M., Kok, J.S., Deayton, J.M., Nowak, R., Adamson, T.M. Sleep. (1993) [Pubmed]
  25. The effect of unilateral somatosensory stimulation on hemispheric asymmetries during slow wave sleep. Cottone, L.A., Adamo, D., Squires, N.K. Sleep. (2004) [Pubmed]
  26. Input of orexin/hypocretin neurons revealed by a genetically encoded tracer in mice. Sakurai, T., Nagata, R., Yamanaka, A., Kawamura, H., Tsujino, N., Muraki, Y., Kageyama, H., Kunita, S., Takahashi, S., Goto, K., Koyama, Y., Shioda, S., Yanagisawa, M. Neuron (2005) [Pubmed]
  27. Arousal effect of orexin A depends on activation of the histaminergic system. Huang, Z.L., Qu, W.M., Li, W.D., Mochizuki, T., Eguchi, N., Watanabe, T., Urade, Y., Hayaishi, O. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  28. Long-term effects of almitrine bismesylate on oxygenation during wakefulness and sleep in chronic obstructive pulmonary disease. Gothe, B., Cherniack, N.S., Bachand, R.T., Szalkowski, M.B., Bianco, K.A. Am. J. Med. (1988) [Pubmed]
  29. Interictal spiking during wakefulness and sleep and the localization of foci in temporal lobe epilepsy. Sammaritano, M., Gigli, G.L., Gotman, J. Neurology (1991) [Pubmed]
  30. Juvenile Parkinson's disease with REM sleep behavior disorder, sleepiness, and daytime REM onset. Rye, D.B., Johnston, L.H., Watts, R.L., Bliwise, D.L. Neurology (1999) [Pubmed]
  31. Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes. Willie, J.T., Chemelli, R.M., Sinton, C.M., Tokita, S., Williams, S.C., Kisanuki, Y.Y., Marcus, J.N., Lee, C., Elmquist, J.K., Kohlmeier, K.A., Leonard, C.S., Richardson, J.A., Hammer, R.E., Yanagisawa, M. Neuron (2003) [Pubmed]
  32. Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects. Xu, Y.L., Reinscheid, R.K., Huitron-Resendiz, S., Clark, S.D., Wang, Z., Lin, S.H., Brucher, F.A., Zeng, J., Ly, N.K., Henriksen, S.J., de Lecea, L., Civelli, O. Neuron (2004) [Pubmed]
  33. Middle-aged men show higher sensitivity of sleep to the arousing effects of corticotropin-releasing hormone than young men: clinical implications. Vgontzas, A.N., Bixler, E.O., Wittman, A.M., Zachman, K., Lin, H.M., Vela-Bueno, A., Kales, A., Chrousos, G.P. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  34. Hyporesponsiveness of the pituitary to CRH during slow wave sleep is not mimicked by systemic GHRH. Antonijevic, I.A., Murck, H., Frieboes, R., Holsboer, T.T., Steiger, A. Neuroendocrinology (1999) [Pubmed]
  35. Characterization of ergot and non-ergot serotonin antagonists by prolactin and growth hormone profiles during wakefulness and sleep. Clarenbach, P., Del Pozo, E., Brownell, J., Heredia, E., Spiegel, R., Cramer, H. Brain Res. (1980) [Pubmed]
  36. Histaminergic descending inputs to the mesopontine tegmentum and their role in the control of cortical activation and wakefulness in the cat. Lin, J.S., Hou, Y., Sakai, K., Jouvet, M. J. Neurosci. (1996) [Pubmed]
  37. Influence of sleep onset on upper-airway muscle activity in apnea patients versus normal controls. Mezzanotte, W.S., Tangel, D.J., White, D.P. Am. J. Respir. Crit. Care Med. (1996) [Pubmed]
  38. Nocturnal and daytime panic attacks--comparison of sleep architecture, heart rate variability, and response to sodium lactate challenge. Sloan, E.P., Natarajan, M., Baker, B., Dorian, P., Mironov, D., Barr, A., Newman, D.M., Shapiro, C.M. Biol. Psychiatry (1999) [Pubmed]
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