Delta sleep-inducing peptide (DSIP) is a naturally occurring substance, which was originally isolated from rabbit brain in 1977 . This curious substance is a nonapeptide that is normally synthesized in the hypothalamus and targets multiple sites including some within the brainstem
Delta-Sleep Inducing Peptide (DSIP)
Delta-sleep inducing peptide (DSIP) was first detected in the cerebral venous blood of rabbits that had been subjected to sleep by electric stimulation of the intralaminal thalamic area. Promotion of SWS after DSIP was reported in several species, although not all preclinical studies reproduced these effects. Only one study has investigated the effects of DSIP on sleep EEG in normal men and found only minor effects. Studies on the efficiency of DSIP in the treatment of insomnia produced conflicting results. DSIP-like immunoreactivity was compared in young men between baseline sleep, sleep deprivation, and recovery sleep. Plasma DSIP-like immunoreactivity decreased at the transition from wakefulness to sleep in both evening sleep and morning recovery sleep. These results suggest that DSIP is induced by mechanisms that are involved in the initiation of sleep.
Endogenous Humoral Factors
Throughout the history of sleep research, diverse factors of endocrine or biochemical origin have been postulated to explain this cycle. Pieron (1913) proposed the existence of substances that, generated during wakefulness, would be removed during the sleep. Investigations carried out in rabbits described a nonapeptide found in the cerebrospinal fluid (CSF) after electrical stimulation of the thalamus that induced sleep (Monnier and Hösli, 1964). Because injection into the brain ventricles of other rabbits provoked delta waves in the EEG, this peptide has been denominated delta sleep-inducing peptide. In most of the subsequent studies, this factor has showed only a mild hypnogenic effect. On the other hand, just like any other peptide, its normal passage through the hematoencephalic barrier is, in any case, difficult and slow.
Peptides derived from the propiomelanocortin and peptides immunologically active have also been proposed as hypnoinducers. More recently, two types of sleep-facilitator peptides have been proposed: (1) SWS promoting substances, such as growth hormone releasing hormone, interleukin-1β, tumour necrosis factor α, adenosine and prostagalndine D2; and (2) PS-promoting substances, such as vasoactive intestinal polypeptide and prolactin. All these substances have fulfilled the criteria for sleep regulatory substances (Krueger and Obal, 1994; Obal and Krueger, 2005).
Hypnogenic actions are attributed nowadays to melatonin. Recent studies have demonstrated that this hormone, known for its chronobiotic effects for a long time, might also have an effect on sleep, causing it to decrease its latency and increase its efficiency (Cardinali, 2005).
The amount of substances that have been described in recent decades permit us to conclude that none of them has a powerful and determinant action, neither can they be attributed a sleep-provoking effect with physiological characteristics acting isolated. Perhaps the encompassed physiological actions of many of them generate a global modulation thus creating a situation favourable to sleep.