Delta sleep-inducing peptide (DSIP): Research
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Delta sleep-inducing peptide (DSIP) is a nonapeptide with the sequence Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, initially isolated from rabbit cerebral venous blood by the Schoenenberger-Monnier group in 1977. DSIP was named for its ability to induce slow-wave sleep (SWS) or delta sleep, characterized by enhanced delta and spindle electroencephalogram (EEG) activity.[1-2]
Despite its name, the role of DSIP in sleep regulation remains controversial. Early studies demonstrated that synthetic DSIP could significantly enhance delta EEG activity in rabbits, suggesting a sleep-promoting effect.[1-2] However, subsequent research has failed to consistently replicate these findings, and the exact mechanism of DSIP's action remains unclear. The peptide has not been conclusively linked to a specific receptor or gene, which complicates the understanding of its biological activity.[3]
DSIP has been studied for various potential therapeutic applications beyond sleep induction. For instance, it has shown promise in stress protection and adaptation, possibly through its effects on mitochondrial respiration and oxidative phosphorylation in rat brain mitochondria.[4] DSIP has also been investigated for its antiepileptic properties, demonstrating a reduction in seizure severity and incidence in metaphit-provoked seizures in rats.[5]
Recent studies have explored DSIP's pharmacological effects in insomnia models. A fusion protein containing DSIP, human serum albumin, and a protein transduction domain was shown to enhance the hypnotic effects of pentobarbital in mice, reducing sleep latency and prolonging sleep duration.[6] Another study indicated that DSIP fusion peptides could modulate neurotransmitter levels and improve sleep in a p-chlorophenylalanine-induced insomnia mouse model.[7]
Additionally, DSIP has been evaluated for its potential to improve sleep architecture and cognitive function under high-altitude conditions. Phosphorylated DSIP (p-DSIP) was found to enhance non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, as well as restore spatial memory in rats exposed to chronic hypobaric hypoxia.[8]
Clinical trials in humans have yielded mixed results. A double-blind study in chronic insomniac patients showed that DSIP administration led to higher sleep efficiency and shorter sleep latency compared to placebo, although the effects were weak and not consistently significant across all measures.[9] Another study investigated DSIP as an adjunct to isoflurane anesthesia, finding that DSIP altered EEG patterns and heart rate variability, but paradoxically reduced delta rhythm and increased bispectral index (BIS), suggesting a decrease in anesthetic depth.[10]
In summary, while DSIP has demonstrated various biological activities, its role in sleep regulation remains uncertain. The peptide's potential therapeutic applications, including stress protection, antiepileptic effects, and sleep enhancement in specific conditions, warrant further investigation. The current consensus in the medical literature is that DSIP's sleep-promoting effects are not well-established, and its mechanism of action is still unresolved.[3]
1. The Delta EEG (Sleep)-Inducing Peptide (DSIP). XI. Amino-Acid Analysis, Sequence, Synthesis and Activity of the Nonapeptide. Schoenenberger GA, Maier PF, Tobler HJ, Wilson K, Monnier M. Pflugers Archiv : European Journal of Physiology. 1978;376(2):119-29. doi:10.1007/BF00581575.
2. Characterization of a Delta-Electroencephalogram (-Sleep)-Inducing Peptide.
Schoenenberger GA, Monnier M. Proceedings of the National Academy of Sciences of the United States of America. 1977;74(3):1282-6. doi:10.1073/pnas.74.3.1282. Leading Journal
3. Delta Sleep-Inducing Peptide (DSIP): A Still Unresolved Riddle. Kovalzon VM, Strekalova TV. Journal of Neurochemistry. 2006;97(2):303-9. doi:10.1111/j.1471-4159.2006.03693.x.
4. Delta Sleep Inducing Peptide (DSIP): Effect on Respiration Activity in Rat Brain Mitochondria and Stress Protective Potency Under Experimental Hypoxia. Khvatova EM, Samartzev VN, Zagoskin PP, Prudchenko IA, Mikhaleva II. Peptides. 2003;24(2):307-11. doi:10.1016/s0196-9781(03)00040-8.
5. Antiepileptic Activity of Delta Sleep-Inducing Peptide and Its Analogue in Metaphit-Provoked Seizures in Rats. Stanojlović OP, Zivanović DP, Mirković SD, Mikhaleva II. Seizure. 2005;14(4):240-7. doi:10.1016/j.seizure.2005.02.001.
6. Expression and Purification of Delta Sleep-Inducing Peptide Fused With Protein Transduction Domain and Human Serum Albumin in Pichia Pastoris.
Zhang XG, Wang WN, Zhang CS, et al. Protein and Peptide Letters. 2017;24(7):668-675. doi:10.2174/0929866524666170426113022.
7. Pichia Pastoris Secreted Peptides Crossing the Blood-Brain Barrier and DSIP Fusion Peptide Efficacy in PCPA-induced Insomnia Mouse Models.
Mu X, Qu L, Yin L, et al. Frontiers in Pharmacology. 2024;15:1439536. doi:10.3389/fphar.2024.1439536. New Research
8. Phosphorylated Delta Sleep Inducing Peptide Restores Spatial Memory and P-Creb Expression by Improving Sleep Architecture at High Altitude. Roy K, Chauhan G, Kumari P, et al. Life Sciences. 2018;209:282-290. doi:10.1016/j.lfs.2018.08.026.
9. Effects of Delta Sleep-Inducing Peptide on Sleep of Chronic Insomniac Patients. A Double-Blind Study. Bes F, Hofman W, Schuur J, Van Boxtel C. Neuropsychobiology. 1992;26(4):193-7. doi:10.1159/000118919.
10. Delta Sleep-Inducing Peptide Alters Bispectral Index, the Electroencephalogram and Heart Rate Variability When Used as an Adjunct to Isoflurane Anaesthesia. Pomfrett CJ, Dolling S, Anders NR, et al.