Biochemical regulation of non-rapid-eye-movement sleep

Abstract

The concept, that sleep regulatory substances (sleep factors) exist, stems from classical endocrinology and is supported by positive transfer experiments in which tissue fluids obtained from sleepy or sleeping animals elicited sleep when injected into recipient animals. The transfer experiments concluded with the identification of four sleep factors: delta sleep-inducing peptide (DSIP), uridine, oxidized glutathione, and a muramyl peptide. A physiological sleep regulatory role, however, has not been determined for these substances. In contrast, transfer experiments did not play a part in the development of the strong experimental evidence that implicated the currently known sleep factors in sleep regulation. These substances include adenosine, prostaglandin D2 (PGD2), growth hormone-releasing hormone (GHRH), interleukin-1 (IL1) and tumor necrosis factor (TNF). They promote non-REMS in various species, inhibition of their action or endogenous production results in loss of spontaneous sleep, and their synthesis and/or release display variations correlating with sleep-wake activity. Although the source of these substances vary they all enhance sleep by acting in the basal forebrain/anterior hypothalamus--preoptic region. It is also characteristic of these substances that they interact in multiple ways often resulting in mutual stimulation or potentiation of each other. Finally, there is a third group of substances whose significance in sleep regulation is less clear but for which there are two or more lines of evidence suggesting that they may have a role in modulating non-REM sleep (NREMS). This group includes oleamide, cortistatin, cholecystokinin (CCK), insulin, and nitric oxide (NO). More sleep regulatory substances are likely to be discovered in the future although it is a long and difficult process requiring multiple laboratories to generate sufficient convincing data to implicate any one of them in sleep regulation.

Sleep and quality of life improvements after endoscopic sinus surgery in patients with chronic rhinosinusitis

“…38 There is a considerable amount of literature linking sleep regulatory peptides in CRS and sleep regulation suggesting plausibility of an immune-brain connection. 39 The mechanisms by which this immune-brain connections occurs is currently being heavily investigated; although preliminary evidence suggests cytokines either act in the brain directly by passage across the blood brain barrier, stimulate afferent transmission, or alter the level or activity of another substance that subsequently signals the brain. 4041 We posit that the decline in local cytokines following sinus surgery may be one factor that is driving the improvements in sleep quality, but at present this remains conjecture.…”

Delta Wave Power: An Independent Sleep Phenotype or Epiphenomenon?

“…18,19 Benzodiazepines enhance NREMS but inhibit EEG δ power. 20 Several sleep regulatory substances enhance duration of NREMS and EEG δ power, e.g., tumor necrosis factor (TNF), growth hormone releasing hormone, interleukin-1 (IL1) (reviewed 21 ), while others decrease EEG δ power while increasing the duration of NREMS, e.g., nerve growth factor, neurotrophin-4, blood flow (to accommodate use-dependent cellular respiration) affects EEG δ power. Peripheral tactile stimulation-induced neural activity leads to increased EEG δ power in subsequent NREMS in the contralateral somatosensory cortex.…”

Sleep Characteristics in Children with Growth Hormone Deficiency

“…GHRH promotes non-REM sleep in humans, rats, mice and rabbits [38]. In most studies, both the duration of SWS and the intensity of slow-wave activity are increased by GHRH.…”

“…The stimulation of nocturnal GH release and the stimulation of SWS reflect, to a large extent, synchronous activity of at least two populations of hypothalamic GHRH neurons [16,38]. …”

“…In most studies, both the duration of SWS and the intensity of slow-wave activity are increased by GHRH. In rats, intracerebral as well as systemic injections of GHRH stimulate non-REM sleep, even in hypophysectomized animals [38]. …”