Abstract
ACETYLCHOLINE (ACh) plays a key role in the transitions between the different phases of sleep1: Slow-wave sleep requires low ACh concentrations in the brain, whereas rapid-eye-movement (REM) sleep is associated with high levels of ACh. Also, these phases of sleep are differentially sensitive to a number of endogenous neuropeptides and cytokines, including somatostatin, which has been shown to increase REM sleep without significantly affecting other phases2. Here we report the cloning and initial characterization of cortistatin, a neuropeptide that exhibits strong structural similarity to somatostatin, although it is the product of a different gene. Administration of cortistatin depresses neuronal electrical activity but, unlike somatostatin, induces low-frequency waves in the cerebral cortex and antagonizes the effects of acetylcholine on hippocampal and cortical measures of excitability. This suggests a mechanism for cortical synchronization related to sleep.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Shiromani, P. J., Gillin, J. C. & Henriksen, S. J. A. Rev. Pharmac. Toxicol. 27, 137–56 (1987).
Borbely, A. A. & Tobler, I. Physiol. Rev. 69, 605–670 (1989).
Glushankov, P. et al. Proc. natn. Acacf. Sci. U.S.A. 81, 6662–6666 (1984).
Veber, D. F. et al. Nature 280, 512–514 (1979).
Erlander, M. G. et al. Neuron 7, 91–100 (1991).
Schonbrunn, A. H. & Tashijan, A. J. R., J. biol. Chem. 235, 6473–6483 (1978).
Halliwell, J. V. & Adams, P. R. Brain Res. 250, 71–92 (1982).
Moore, S. D. et al. Science 239, 278–280 (1988).
Schweitzer, P., Madamba, S. & Siggins, G. R. Nature 346, 464–466 (1990).
Andersen, P., Bliss, T. V. P. & Skrede, K. K. Expl Brain Res. 13, 208–221 (1971).
Danguir, J. Brain Res. 367, 26–30 (1986).
Steriade, M., McCormick, D. A. & Sejnowski, T. J. Science 262, 679–685 (1993).
Andersen, P., Eccles, J. C. & Løyning, Y. J. Neurophysiol. 27, 607–619 (1964).
Kandel, E. R. & Spencer, W. A. J. Neurophysiol. 24, 243–259 (1961).
Steffensen, S. & Henriksen, S. J. Brain Res. 538, 46–53 (1991).
Maurer, R. et al. Proc. natn. Acad. Sci. U.S.A. 79, 4815–4817 (1982).
Scharfman, H. E. & Schwartzkroin, P. A. Brain Res. 493, 205–211 (1989).
deLecea, L. et al. Molec. Brain Res. 25, 286–296 (1994).
Schweitzer, P. et al. J. Neurosci. 13, 2033–2049 (1993).
Prospero-Garcia, O., Criado, J. R. & Henriksen, S. J. Pharmac. Biochem. Behav. 49, 413 (1994).
Steffensen, S. C., Campbell, I. L. & Henriksen, S. J. Brain Res. 652, 149 (1994).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
de Lecea, L., Criado, J., Prospero-Garcia, Ó. et al. A cortical neuropeptide with neuronal depressant and sleep-modulating properties. Nature 381, 242–245 (1996). https://doi.org/10.1038/381242a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/381242a0
- Springer Nature Limited
This article is cited by
-
Cortistatin deficiency reveals a dysfunctional brain endothelium with impaired gene pathways, exacerbated immune activation, and disrupted barrier integrity
Journal of Neuroinflammation (2023)
-
Somatostatin slows Aβ plaque deposition in aged APPNL-F/NL-F mice by blocking Aβ aggregation
Scientific Reports (2023)
-
Development of a novel vasculogenic mimicry-associated gene signature for the prognostic assessment of osteosarcoma patients
Clinical and Translational Oncology (2023)
-
Evaluation Anti-inflammatory Effect of Conjugated Gold Nanoparticles with Cortistatin Peptide as Drug Delivery to Asthmatic Lung Tissue
International Journal of Peptide Research and Therapeutics (2023)
-
Structure-based design of a Cortistatin analogue with immunomodulatory activity in models of inflammatory bowel disease
Nature Communications (2021)