Delta Sleep-Inducing Peptide in the Rat Brain: An Immunohistological Microscopic Study

Abstract

The authors have developed a method which makes it possible, for the first time, to visualize the delta sleep-inducing peptide in histological preparations and study it under the light and fluorescence microscope. Their research builds on Monnier’s discovery, in 1963, of a humoral hypnogenic factor in rabbits which was subsequently isolated and identified as a nonapeptide. Dubbed delta sleep-inducing peptide (DSIP), this factor was later detected in rat brain by radioimmunoassay but has eluded histological visualization until recently. In their work, the authors used an anti-DSIP antiserum suitable for immunohistological purposes. Two indirect immunohistological methods (PAP and immunofluorescence) allowed them to visualize, for the first time, structures containing specific DSIP-like immunoreactivity in some areas of the rat brain: indusium griseum, nucleus septi lateralis, hippocampus, striae longitudinales of Lancisi, bandeletta diagonalis of Broca, pallidum, hypothalamus, hypophysis and neocortex. Some DSIP pathways seem likely: (1) indusium griseum – striae longitudinales – hippocampus; (2) nucleus septi lateralis – striae longitudinales, bandeletta diagonalis – hippocampus; (3) neurons of the pyramidal layer of the hippocampus – gyms dentatus; (4) pallidum – commissura of Ganser – hypothalamus. The possible correlations between DSIP neurons and neurons with other neurotransmitters are discussed. In preliminary clinical trials, DSIP has shown promise for the treatment of insomnia and the opiate and alcohol withdrawal syndromes. Apart from the influence of DSIP on sleep and its possible role in addiction, the authors discuss the part which may be played by the limbic DSIP systems in instinctive-affective and memory mechanisms, and their possible involvement in psychosis and Alzheimer’s disease. Studies on DSIP have opened up new perspectives for research on the mechanisms of sleep, memory, drug addiction"(and possibly even of psychosis and Alzheimer’s disease) and their treatment.

Successful Treatment of Withdrawal Symptoms with Delta Sleep-Inducing Peptide, a Neuropeptide with Potential Agonistic Activity on Opiate Receptors

“…Indeed, experiments proving a specific binding of DSIP to endorphin receptors are lack ing so far. However, our group has demonstrated its pres ence in nerve tissue by immunofluorescence techniques [6], On the other hand, experiments by Kastin et al [7] with a radioimmunoassay tend to prove that the sites of DSIP's maximal concentration coincide with the sites of maximal concentration of endorphin receptors.…”

Immunoreactive Delta Sleep-Inducing Peptide in Pituitary Adrenocorticotropin/Alpha-Melanotropin Cells and Adrenal Medullary Cells of the Pig

“…In addition, D SIP has been shown to inhibit the release and actions of corticotropin-releasing factor (C'RF) [11 ,22,33]. In man, ef fects on higher mental functions o f synthetic D SIP injected intravenously have also been described [26], DSIP-like immunoreactivity has been demonstrated by radioimmunoassay (RIA) and immunocytochemistry in the rat central nervous system [4,8,9], and by R IA in several peripheral organs of the rat, including the adrenals [10] as well as in plasma o f several mammals [1.9, 12]. The exact nature of the immunoreactive material in tissue extracts and body fluids is still a matter of discussion [7 ,9 ,1 0 ,12].…”

Effects of Delta-Sleep-Inducing Peptide on 24-Hour Sleep-Wake Behaviour in Severe Chronic Insomnia

“…Alternatively, intermediate-term treat ment possibly accumulates the actions of DSIP on brain functions and thus induces fundamental changes of physiological mech anisms. The theory that the neuropeptide DSIP is an endogenous neuromodulator of sleep has recently obtained further support by finding DSIP-containing cells and path ways in the limbic system and hypothalamus [24], binding sites for DSIP in the nucleus reticularis giganto-cellularis of the brain stem, a structure involved in the regulation of the sleep-wakefulness rhythm [25], and excitatory actions of DSIP at the single-neu ron level of this structure [26]. On this back ground it seems likely that DSIP administra tion reinforces normal physiological func tions.…”