The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Conditional Ablation of Orexin/Hypocretin Neurons: A New Mouse Model for the Study of Narcolepsy and Orexin System Function
Open accessAbstract
The sleep disorder narcolepsy results from loss of hypothalamic orexin/hypocretin neurons. Although narcolepsy onset is usually postpubertal, current mouse models involve loss of either orexin peptides or orexin neurons from birth. To create a model of orexin/hypocretin deficiency with closer fidelity to human narcolepsy, diphtheria toxin A (DTA) was expressed in orexin neurons under control of the Tet-off system. Upon doxycycline removal from the diet of postpubertal orexin-tTA;TetO DTA mice, orexin neurodegeneration was rapid, with 80% cell loss within 7 d, and resulted in disrupted sleep architecture. Cataplexy, the pathognomic symptom of narcolepsy, occurred by 14 d when ∼5% of the orexin neurons remained. Cataplexy frequency increased for at least 11 weeks after doxycycline. Temporary doxycycline removal followed by reintroduction after several days enabled partial lesion of orexin neurons. DTA-induced orexin neurodegeneration caused a body weight increase without a change in food consumption, mimicking metabolic aspects of human narcolepsy. Because the orexin/hypocretin system has been implicated in the control of metabolism and addiction as well as sleep/wake regulation, o rexin-tTA; TetO DTA mice are a novel model in which to study these functions, for pharmacological studies of cataplexy, and to study network reorganization as orexin input is lost.
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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-citationThe hypocretins: hypothalamus-specific peptides with neuroexcitatory activity
de Lecea, L., Kilduff, T. S., Peyron, C., Gao, X.-B., Foye, P. E., Danielson, P. E., Fukuhara, C., Battenberg, E. L. F., Gautvik, V. T., Bartlett, F. S., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.1.322 · Cited by 3,878 · cited 1×
“The etiology of narcolepsy is a loss of the hypothalamic neurons that express the orexin/hypocretin neuropeptides (Sakurai et al., 1998; de Lecea et al., 1998).”
BackgroundSelf-citationMicroglia: Active sensor and versatile effector cells in the normal and pathologic brain
Hanisch, U.-K., & Kettenmann, H. (2007) · Nature Neuroscience · doi:10.1038/nn1997 · Cited by 3,676
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
Hypothalamic orexin (hypocretin) neurons express vesicular glutamate transporters VGLUT1 or VGLUT2
Rosin, D. L., Weston, M. C., Sevigny, C. P., Stornetta, R. L., & Guyenet, P. G. (2003) · Journal of Comparative Neurology · doi:10.1002/cne.10860 · Cited by 252
Cited by
The neurobiological basis of narcolepsy
Mahoney, C. E., Cogswell, A., Koralnik, I. J., & Scammell, T. E. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0097-x · Cited by 289
Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals
Kumar Jha, P., Challet, E., & Kalsbeek, A. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.01.024 · Cited by 235
REM sleep-active MCH neurons are involved in forgetting hippocampus-dependent memories
Izawa, S., Chowdhury, S., Miyazaki, T., Mukai, Y., Ono, D., Inoue, R., Ohmura, Y., Mizoguchi, H., Kimura, K., Yoshioka, M., et al. (2019) · Science · doi:10.1126/science.aax9238 · Cited by 224
Self-citationHolt, M. K., Richards, J. E., Cook, D. R., Brierley, D. I., Williams, D. L., Reimann, F., Gribble, F. M., & Trapp, S. (2019) · Diabetes · doi:10.2337/db18-0729 · Cited by 212
The Neurobiology of Sleep and Wakefulness
Schwartz, M. D., & Kilduff, T. S. (2015) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2015.07.002 · Cited by 207
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Metadata
- Authors
- Tabuchi, S., Tsunematsu, T., Black, S. W., Tominaga, M., Maruyama, M., Takagi, K., Minokoshi, Y., Sakurai, T., Kilduff, T. S., & Yamanaka, A.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2014-05-07
- Volume
- 34
- Issue
- 19
- Pages
- 6495-6509
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2051674121
- Cited by
- 218
- References
- 5
- FWCI
- 11.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Tabuchi, S., Tsunematsu, T., Black, S. W., Tominaga, M., Maruyama, M., Takagi, K., Minokoshi, Y., Sakurai, T., Kilduff, T. S., & Yamanaka, A. (2014). Conditional Ablation of Orexin/Hypocretin Neurons: A New Mouse Model for the Study of Narcolepsy and Orexin System Function. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.0073-14.2014
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