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Molecular Mechanisms of Sleep and Wakefulness
Author(s) -
Mackiewicz Miroslaw,
Naidoo Nirinjini,
Zimmerman John E.,
Pack Allan I.
Publication year - 2008
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1417.030
Subject(s) - wakefulness , sleep (system call) , neuroscience , medicine , psychology , electroencephalography , computer science , operating system
Major questions on the biology of sleep include the following: what are the molecular functions of sleep; why can wakefulness only be sustained for defined periods before there is behavioral impairment; what genes contribute to the individual differences in sleep and the response to sleep deprivation? Behavioral criteria to define sleep have facilitated identification of sleep states in a number of different model systems: Drosophila , zebrafish, and Caenorhabditis elegans . Each system has unique strengths. Studies in these model systems are identifying conserved signaling mechanisms regulating sleep that are present in mammals. For example, the PKA‐CREB signaling mechanism promotes wakefulness in Drosophila , mice, and C. elegans . Microarray studies indicate that genes whose expression is upregulated during sleep are involved in macromolecule biosynthesis (proteins, lipids [including cholesterol], heme). Thus, a key function of sleep is likely to be macromolecule synthesis. Moreover, in all species studied to date, there is upregulation of the molecular chaperone BiP with extended wakefulness. Sleep deprivation leads to cellular ER stress in brain and the unfolded protein response. Identification of genes regulating sleep has the potential for translational studies to elucidate the genetics of sleep and response to sleep deprivation in humans.