The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice
Open accessAbstract
Narcolepsy-cataplexy is a neurological disorder associated with the inability to maintain wakefulness and abnormal intrusions of rapid eye movement sleep-related phenomena into wakefulness such as cataplexy. The vast majority of narcoleptic-cataplectic individuals have low or undetectable levels of orexin (hypocretin) neuropeptides in the cerebrospinal fluid, likely due to specific loss of the hypothalamic orexin-producing neurons. Currently available treatments for narcolepsy are only palliative, symptom-oriented pharmacotherapies. Here, we demonstrate rescue of the narcolepsy-cataplexy phenotype of orexin neuron-ablated mice by genetic and pharmacological means. Ectopic expression of a prepro-orexin transgene in the brain completely prevented cataplectic arrests and other abnormalities of rapid eye movement sleep in the absence of endogenous orexin neurons. Central administration of orexin-A acutely suppressed cataplectic behavioral arrests and increased wakefulness for 3 h. These results indicate that orexin neuron-ablated mice retain the ability to respond to orexin neuropeptides and that a temporally regulated and spatially targeted secretion of orexins is not necessary to prevent narcoleptic symptoms. Orexin receptor agonists would be of potential value for treating human narcolepsy.
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Sakurai, T., Amemiya, A., Ishii, M., Matsuzaki, I., Chemelli, R. M., Tanaka, H., Williams, S. C., Richardson, J. A., Kozlowski, G. P., Wilson, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)80949-6 · Cited by 5,501
Self-citationNeurons containing hypocretin (orexin) project to multiple neuronal systems
Peyron, C., Tighe, D. K., van den Pol, A. N., de Lecea, L., Heller, H. C., Sutcliffe, J. G., & Kilduff, T. S. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-23-09996.1998 · Cited by 3,466
Narcolepsy in orexin Knockout Mice
Chemelli, R. M., Willie, J. T., Sinton, C. M., Elmquist, J. K., Scammell, T., Lee, C., Richardson, J. A., Williams, S. C., Xiong, Y., Kisanuki, Y., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)81973-x · Cited by 3,095
Self-citationReduced Number of Hypocretin Neurons in Human Narcolepsy
Thannickal, T. C., Moore, R. Y., Nienhuis, R., Ramanathan, L., Gulyani, S., Aldrich, M., Cornford, M., & Siegel, J. M. (2000) · Neuron · doi:10.1016/s0896-6273(00)00058-1 · Cited by 2,089
Hypocretin (orexin) deficiency in human narcolepsy
Nishino, S., Ripley, B., Overeem, S., Lammers, G. J., & Mignot, E. (2000) · The Lancet · doi:10.1016/s0140-6736(99)05582-8 · Cited by 1,776
Effects of orexin-A on memory processing
Jaeger, L. B., Farr, S. A., Banks, W. A., & Morley, J. E. (2002) · Peptides · doi:10.1016/s0196-9781(02)00110-9 · Cited by 116
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Control of sleep and wakefulness
Brown, R. E., Basheer, R., McKenna, J. T., Strecker, R. E., & McCarley, R. W. (2012) · Physiological Reviews · doi:10.1152/physrev.00032.2011 · Cited by 1,477
The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness
Sakurai, T. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2092 · Cited by 1,276
Self-citationPromotion of sleep by targeting the orexin system in rats, dogs and humans
Brisbare-Roch, C., Dingemanse, J., Koberstein, R., Hoever, P., Aissaoui, H., Flores, S., Mueller, C., Nayler, O., van Gerven, J., de Haas, S. L., et al. (2007) · Nature Medicine · doi:10.1038/nm1544 · Cited by 573
Hypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish
Prober, D. A., Rihel, J., Onah, A. A., Sung, R.-J., & Schier, A. F. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4332-06.2006 · Cited by 508
Tranah, G. J., Blackwell, T., Stone, K. L., Ancoli‐Israel, S., Paudel, M. L., Ensrud, K. E., Cauley, J. A., Redline, S., Hillier, T. A., Cummings, S. R., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22468 · Cited by 525
Metadata
- Authors
- Mieda, M., Willie, J. T., Hara, J., Sinton, C. M., Sakurai, T., & Yanagisawa, M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-03-16
- Volume
- 101
- Issue
- 13
- Pages
- 4649-4654
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1900979097
- Cited by
- 341
- References
- 6
- FWCI
- 9.76
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice. https://app.cochat.ai/papers/10.1073/pnas.0400590101
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- Mieda, M., Willie, J. T., Hara, J., Sinton, C. M., Sakurai, T., & Yanagisawa, M. (2004). Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0400590101
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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