Orexin narcolepsy-cataplexy

Orexins in sleep and wakefulness rodent models of narcolepsy-cataplexy... 

The cause of the orexin-containing cell loss in typical narcolepsy-cataplexy remains unknown, but the HLA association is intriguing because it suggests that autoimmunity could mediate a central disease process. This is not... 

The phenotypic characterization of genetically modified rodents has advanced the understanding of both the basis of narcolepsy-cataplexy and the functions of the orexin system in the normal animal. Here we review the... 

Severe narcolepsy-cataplexy indistinguishable from orexin mice... 

Beuckmann, C. T., Sinton, C. M., Williams, S. C. et al. (2004). Expression of a poly-glutamine-ataxin-3 transgene in orexin neurons induces narcolepsy-cataplexy in the rat. J. Neurosci 24, 4469-77. 

Mieda, M. Yanagisawa, M. (2006). Rodent models of narcolepsy-cataplexy. In The Orexin/Hypocretin System Physiology and Pathophysiology, ed. S. Nishino T. Sakurai, Totowa, NJ Humana Press, pp. 255-66. 

Willie, J. T. Yanagisawa, M. (2007). Lessons from sleepy mice narcolepsy-cataplexy and the orexin neuropeptide system. In Narcolepsy and Hypersomnia, ed. C. Bassetti, M. Billiard E. Mignot, New York, NY Informa Healthcare, pp. 257-78. 

Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and cataplexy, may be caused by the lack of hypocretin mRNA and peptides in humans (Peyron et al., 2000) or a disruption of the hypocretin receptor 2 or its ligand in dogs and mice (Lin et al., 1999 Chemelli et al., 1999). Hypocretin-containing neurons are located exclusively in the dorsomedial, lateral, and perifornical hypothalamic areas (Peyron et al., 1998). Two hypocretin sequences, Hcrt-1 (orexin-A) and Hcrt-2 (orexin-B), are generated from a single preprohypocretin (De Lecea et al., 1998 Peyron et al, 1998 Sakurai et al, 1998). Axons from these neurons are found in the hypothalamus, locus coeruleus (LC), raphe nuclei, tuberomamillary nucleus, midline thalamus, all levels of spinal cord, sympathetic and parasympathetic centers, and many other brain regions... 

Mieda, M., Willie, J. T., Hara, J. et al (2004b). Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice. Proc. Natl. Acad. Scl USA 101, 4649-54. 

Kanbayashi T, Inoue Y, Chiba S, Aizawa R, Saito Y, Tsukamoto H, Fujii Y, Nishino S, Shimizu T (2002) CSF hypocretin-1 (orexin-A) concentrations in narcolepsy with and without cataplexy and idiopathic hypersomnia. J Sleep Res 11 91-93... 

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