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Excessive Daytime Sleepiness: Clinical Considerations
Published in Anthony N. Nicholson, The Neurosciences and the Practice of Aviation Medicine, 2017
Thomas C. Britton, Andrew R. C. Cummin, Anthony N. Nicholson
Ninety per cent of patients with narcolepsy with cataplexy have absent or low concentrations of hypocretin (orexin) in the cerebrospinal fluid (Bourgin et al., 2008). Hypocretin is a neuropeptide produced in the posterolateral hypothalamus that has been shown to play a part in arousal, muscle tone and locomotion, the regulation of feeding behaviour and autonomic functions. Its role in the control of REM sleep remains controversial, but it probably acts as a sleep–wake stabilizer, preventing sudden and inappropriate transitions between REM and orthodox sleep. Those with narcolepsy with cataplexy appear to have a selective loss of the hypocretin-producing cells within the posterolateral hypothalamus.
Factors Affecting Mnemonic Performance in a Nonhuman Primate Model of Cognitive Workload
Published in Steven Kornguth, Rebecca Steinberg, Michael D. Matthews, Neurocognitive and Physiological Factors During High-Tempo Operations, 2018
Robert E. Hampson, Sam A. Deadwyler
Another important receptor system involved in sleep-waking cycles is the Orexin-A/Hypocretin-1 system. The agonist peptide orexin has been shown to prevent sleep in narcoleptic dogs and has also been shown to release glutamate (Siegel 2004). Consequently, the sleep preventing effects of orexin may be potentiated by CX717. Ampakines, therefore, have the capability to positively modulate many different glutamatergic circuits and pathways in several pertinent brain regions (Lynch 2002), thereby increasing the potential to counteract cognitive deficits under normal as well as sleep deprived conditions (Drummond and Brown 2001, Smith, McEvoy, and Gevins 2002, Thomas et al. 2000, and Ferrara et al. 2000).
Treatment Options for Chemical Sensitivity
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 5, 2017
William J. Rea, Kalpana D. Patel
Ties between circadian disruption and metabolic disturbance have garnered attention, including large cross-sectional sampling of populations subjected to shift work. Extensive studies also indicate a correlation between sleep time and body mass index (BMI). Disruption in specific phases of sleep may be connected to metabolic function. Subtle tones sufficient to selectively deprive subjects of slow wave sleep without producing conscious wakefulness were sufficient to impair glucose tolerance.88 Neuroanatomic studies also indicate interconnections between regions of hypothalamus important in circadian signaling, energetics, and sleep.89,90 At the molecular level, orexin (hypocretin), originally discovered as a neuropeptide produced in the feeding-stimulatory neurons of lateral hypothalamus, is positioned at the intersection of neuronal systems controlling sleep, circadian output, and metabolism.90 Analysis of orexin receptor 2 knockout mice indicates that lack of orexin signaling increases susceptibility to obesity (rather than the original expectation that orexin, a potent wakefulness-inducing peptide, would induce adiposity).91 Orexin receptor 2 mutations also account for canine narcolepsy, and orexin deficiency is a hallmark of the disease in humans.92 Activity of the orexin neuron is modulated by glucose and integrates signals downstream of leptin-responsive neurons within the arcuate nucleus. Leptin also impacts sleep, possibly independently of effects on body weight, raising the need to further define leptin actions in this process.93 Manipulation of orexin signaling, an integrator of energetic and circadian signals, may, thus, provide opportunities to intervene not only in disorders of sleep but also related metabolic complications.
Clinical translation of biomedical sensors for sports medicine
Published in Journal of Medical Engineering & Technology, 2019
Dhruv R. Seshadri, Samantha Magliato, James E. Voos, Colin Drummond
Biosensors have been used to detect stress and changes in mental acuity by measuring a wide array of biomarkers such as Orexin-A [56], dopamine [57], and interleukin-6 (IL-6) [58]. Orexin peptides and their respective receptors in the brain are imperative in regulating feeding, autonomic control, sleep, attention, stress, and memory [56]. Measuring such a neuropeptide non-invasively utilising functionalised semiconductors decorated with antibodies or peptides could serve to be considered a breakthrough in the wearables field for high-specificity and high-accuracy detection [59,60]. On that note, researchers utilised interdigitated Zinc Oxide Field Effect Transistors (ZnO FETs) to detect Orexin A in vitro by binding a bifunctional peptide to both the ZnO semiconductor and the neuropeptide [56]. The neuropeptide-FET binding was transmitted into an electrical signal and the sensor selectivity was able to detect to about 100 aM concentration in water, 10 fM in filtered human saliva, and 1 nM in filtered foetal bovine serum [56]. Further work is needed for the real-time detection of such biomarkers, improved sensor sensitivity, and stability.