Increasing length of wakefulness and modulation of hypocretin-1 in the wake-consolidated squirrel monkey
Abstract
The neuropeptides hypocretins (orexins), the loss of which results in the sleep disorder narcolepsy, are hypothesized to be involved in the consolidation of wakefulness and have been proposed to be part of the circadian-driven alertness signal. To elucidate the role of hypocretins in the consolidation of human wakefulness we examined the effect of wake extension on hypocretin-1 in squirrel monkeys, primates that consolidate wakefulness during the daytime as do humans. Wake was extended up to 7 h with hypocretin-1, cortisol, ghrelin, leptin, locomotion, and feeding, all being assayed. Hypocretin-1 ( P < 0.01), cortisol ( P < 0.001), and locomotion ( P < 0.005) all increased with sleep deprivation, while ghrelin ( P = 0.79) and leptin ( P = 1.00) did not change with sleep deprivation. Using cross-correlation and multivariate modeling of these potential covariates along with homeostatic pressure (a measure of time awake/asleep), we found that time of day and homeostatic pressure together explained 44% of the variance in the hypocretin-1 data ( P < 0.001), while cortisol did not significantly contribute to the overall hypocretin-1 variance. Locomotion during the daytime, but not during the nighttime, helped explain < 5% of the hypocretin-1 variance ( P < 0.05). These data are consistent with earlier evidence indicating that in the squirrel monkey hypocretin-1 is mainly regulated by circadian inputs and homeostatic sleep pressure. Concomitants of wakefulness that affect hypocretin-1 in polyphasic species, such as locomotion, food intake, and food deprivation, likely have a more minor role in monophasic species, such as humans.
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Orexin neurons are active during waking and quiescent during sleep; consistently, orexin levels in the CSF are maximal at the end of the waking period.
“Orexin neurons are active during waking and quiescent during sleep; consistently, orexin levels in the CSF are maximal at the end of the waking period.80,81”
From Interacting epidemics? Sleep curtailment, insulin resistance, and obesity (2012) · cites this paper as [81]
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- Authors
- Zeitzer, J. M., Buckmaster, C. L., Lyons, D. M., & Mignot, E.
- Affiliations
- Stanford University (US)
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2007-10
- Volume
- 293
- Issue
- 4
- Pages
- R1736-R1742
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W1971551930
- Cited by
- 31
- References
- 29
- Citations by year
- 2024: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2017: 3 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 4 · 2012: 3
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institute of Mental Health (MH-47573, R01MH047573)
- National Institute of Neurological Disorders and Stroke (NS-23724)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- orexin-A, orexin, sleep deprivation, circadian rhythm, homeostatic sleep pressure, cortisol, ghrelin, leptin, locomotion, feeding, squirrel monkey, alertness, polyphasic sleep
- MeSH terms
- Orexins, Animals, Female, Neuropeptides, Saimiri, Sleep Deprivation, Wakefulness, Leptin, Intracellular Signaling Peptides and Proteins, Ghrelin
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