DSIP

DSIP  Research

What is the research background of DSIP?

In the 1970s, there was a boom in sleep research, and scientists were eager to decipher the mysteries of sleep regulation. In 1977, the Swiss chemist Schönenberg and his team accidentally discovered DSIP while studying the sleep patterns of rabbits. It is a non-peptide composed of nine amino acids, which is produced in the hypothalamus and pituitary gland. During this period, significant breakthroughs were made in peptide science. American scientist Kastin and Dutch scientist de Wied proposed the view that peptides could cross the blood-brain barrier, laying the foundation for subsequent research on DSIP. After all, the brain is tightly protected by the blood-brain barrier, and most substances are difficult to enter. If DSIP can cross this barrier, it will greatly affect its role in the brain's sleep regulation mechanism.

Subsequent studies have found that DSIP exists not only in specific areas of the brain but also in the limbic system in free or bound forms, as well as in a variety of peripheral organs, tissues, and body fluids. For example, in the pituitary gland, it is co-localized with a variety of peptides and non-peptide mediators such as adrenocorticotropic hormone. In intestinal secretory cells and the pancreas, it coexists with glucagon. This widespread distribution suggests that DSIP may have diverse and complex functions. Initially, DSIP was regarded as a sleep peptide. With the deepening of research, it has been found that its impact on the body is not limited to sleep. Some studies have shown that it may play a role in the stress response and pain perception, and has the potential characteristics of relieving anxiety and reducing pain, but these effects still need to be verified by more research.

What is the mechanism of action of DSIP?

Regulation of sleep and wakefulness

Influencing the sleep and wakefulness cycle: A number of studies have shown that DSIP has a significant regulatory effect on sleep and wakefulness. For example, in a study, a 35-year-old male narcolepsy patient was repeatedly injected with DSIP, and was evaluated through self-report, performance tests, multiple sleep latency tests, and all-night polysomnography. It was found that DSIP reduced the frequency of sleep attacks, increased daytime activity, alertness, and performance^[1]. DSIP compressed the sleep cycle and enhanced rapid eye movement (REM) sleep. The results indicate that these effects are due to DSIP enhancing the circadian rhythm and ultradian rhythm. DSIP may promote the physiological mechanisms of peripheral preparation related to sleep onset.

Regulating sleep structure: DSIP not only affects the frequency and duration of sleep but also has an impact on the sleep structure. It can enhance REM sleep, indicating its important role in regulating different stages of sleep.

Physiological effects

Effects on thermoregulation, heart rate, blood pressure, pain threshold, and the lymphokine system: In addition to promoting sleep under specific conditions in animals, DSIP has a variety of physiological effects. For example, DSIP can affect thermoregulation, heart rate, blood pressure, pain threshold, and the lymphokine system ^[2]. These effects of DSIP depend on the circadian rhythm cycle, and some effects appear before the signs of neural or behavioral sleep. This suggests that DSIP may initiate the physiological mechanisms of peripheral preparation before sleep onset.

Antioxidant effect

Studies have found that subcutaneous injection of exogenous DSIP (100μg/kg body weight, injected for 5 consecutive days) in rats aged 2 - 24 months can effectively prevent the oxidative damage of lipids and the accumulation of malondialdehyde in the tissues and plasma of rats of different ages^[4] . DSIP has a powerful antioxidant effect, which is achieved by activating various endogenous antioxidant protection mechanisms in intracellular and intercellular fluids. DSIP has a stimulating effect on the activities of superoxide dismutase, catalase, and ceruloplasmin, and affects the concentrations of non-enzymatic antioxidants such as urea and uric acid. With the physiological aging of organisms, the antioxidant protection mechanisms will be inhibited, while DSIP can increase the ability of the endogenous antioxidant protection system in tissues and blood, mainly by stimulating the components of the enzymatic antioxidant system, especially in the later stage of individual development.

What are the applications of DSIP?

Treatment of insomnia

In a study, DSIP injection treatment was carried out on insomnia patients. The results showed that a single injection of DSIP at a dose of 25nmol/kg body weight before sleep could improve sleep. Repeated administration showed that the sleep structure normalized after four administrations. Repeated injection in the morning, in addition to increasing daytime activity, still had a strong positive impact on nighttime sleep, but the effect of twice-daily dosing was not good. In cases of insomnia caused by organic brain diseases, high doses of DSIP responded well^[1].

Treatment of narcolepsy

A 35-year-old male narcolepsy patient was repeatedly injected with DSIP in a study. The effects of DSIP on wakefulness and sleep were evaluated through self-report, performance tests, multiple sleep latency tests, and all-night polysomnography. The results showed that DSIP reduced the frequency of sleep attacks, increased daytime activity, alertness, and performance. DSIP compressed the sleep time and enhanced REM sleep. The study results indicate that these effects are due to DSIP emphasizing the circadian rhythm and ultradian rhythm^[1].

Treatment of alcohol and opiate withdrawal syndromes

Clinical treatment effects: Based on the results of animal studies, that is, the direct injection of morphine, alcohol, pentobarbital, and DSIP into the bulboreticular formation-midbrain-thalamus recruitment system can induce slow-wave sleep and a large number of spindle waves, and this effect can be reversed by naloxone. It is speculated that DSIP has agonistic activity on opioid receptors and may be valuable in the treatment of withdrawal syndromes[3]. After intravenous injection of DSIP for the treatment of 107 hospitalized patients with alcohol (n = 47) or opiate (n = 60) withdrawal symptoms, the clinical evaluations by doctors and nurses showed that 97% and 87% of opiate and alcohol addicts, respectively, had their clinical symptoms and signs disappear or significantly improve after DSIP administration, and the relief of anxiety symptoms was relatively slow. Opiate addicts had longer-lasting clinical symptoms and required more DSIP injections ^[3].

Which patients can DSIP provide adjuvant effects for?

Patients with sleep disorders: DSIP can induce and regulate sleep. For patients with insomnia, including those with difficulty falling asleep, light sleep, and easy waking up, it may help improve sleep quality, extend sleep time, and help them fall asleep faster and maintain a more stable sleep. In addition, for people whose sleep rhythm is disrupted due to jet lag, shift work, etc., DSIP may also help adjust the sleep cycle and restore a normal sleep pattern.

Patients with nervous system diseases: Some nervous system diseases such as Parkinson's disease and Alzheimer's disease are often accompanied by sleep disorders and abnormal nerve functions. In addition to improving sleep, DSIP may also have a certain protective effect on nerve cells, helping to relieve some symptoms of nervous system diseases and improve the quality of life of patients. For example, in Parkinson's disease patients, improving sleep may help reduce daytime fatigue and movement disorders.

Patients with stress-related diseases: People who are under long-term stress, such as patients with mental and psychological diseases like anxiety disorders and depression, often have sleep problems and their bodies are in a state of chronic stress. DSIP can regulate the body's stress response by regulating sleep, helping to relieve emotional symptoms such as anxiety and depression and improving the overall state of patients. At the same time, for some physical function disorders caused by stress, such as digestive disorders and decreased immune function, DSIP may also play a certain adjuvant improvement role by improving sleep and regulating the stress response.

In conclusion, DSIP plays a key role in the field of sleep regulation. It can effectively improve the sleep quality of insomnia patients and extend their sleep time. For narcolepsy patients, it can reduce the frequency of sleep attacks and improve daytime activity and alertness.

Relevant Citations

[1]  Schneider-Helmert D. Effects of DSIP on narcolepsy[J]. European Neurology, 1984,23(5):353-357.DOI:10.1159/000115713.

[2]  Yehuda S, Carasso R L. DSIP—A tool for investigating the sleep onset mechanism - a review[J]. International Journal of Neuroscience, 1988,38(3-4):345-353.DOI:10.3109/00207458808990695.

[3]  Dick P, Costa C, Fayolle K, et al. DSIP in the treatment of withdrawal syndromes from alcohol and opiates[J]. European Neurology, 1984,23(5):364-371.DOI:10.1159/000115715.

[4]  Bondarenko T I, Maiboroda E A, Mikhaleva I I, et al. Mechanism of geroprotective action of delta-sleep inducing peptide[J]. Advances in Gerontology, 2011,1(4):328-339.DOI:10.1134/S2079057011040035.