Abstract
After the discovery of narcolepsy genes in dogs (hypocretin receptor 2) and mice (prepro-orexin) (1,2), establishing functional assays for hypocretin/orexin status in human cases became a high priority. It is unlikely that these high-penetrant hypocretin-related genes found in animals are involved in most human narcoleptic cases (this was later confirmed by mutation screenings in human narcoleptic subjects including high-risk cases; 3), but functional loss/impairment of hypocretin neurotransmission might be involved.
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References
Chemelli, R.M., Willie, J.T., Sinton, C.M., et al. (1999) Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98, 437–451.
Lin, L., Faraco, J., Li, R., et al. (1999) The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 98, 365–376.
Peyron, C., Faraco, J., Rogers, W., et al. (2000) A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat. Med. 6, 991–997.
Nishino, S., Ripley, B., Overeem, S., et al. (2001) Low CSF hypocretin (orexin) and altered energy homeostasis in human narcolepsy. Ann. Neurol. 50, 381–388.
Nishino, S., Ripley, B., Overeem, S., Lammers, G.J., and Mignot, E. (2000) Hypocretin (orexin) deficiency in human narcolepsy. Lancet 355, 39–40.
Ripley, B., Okura, M., Fujiki, N., Mignot, E., and Nishino, S. (2001) Hypocretin-1 levels in familial and sporadic cases of canine narcolepsy. Neurobiol. Dis. 8, 525–534.
Mignot, E., Lammers, G.J., Ripley, B., et al. (2002) The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch. Neurol. 59, 1553–1562.
Ripley, B., Overeem, S., Fujiki, N., et al. (2001) CSF hypocretin/orexin levels in narcolepsy and other neurological conditions. Neurology 57, 2253–2258.
Dalal, M.A., Schuld, A., Haack, M., et al. (2001) Normal plasma levels of orexin A (hypocretin-1) in narcoleptic patients. Neurology 56, 1749–1751 (Erratum appears in Neurology 2002, 58, 334).
Kanbayashi, T., Inoue, Y., Chiba, S., et al. (2002) CSF hypocretin-1 (orexin-A) concentrations in narcolepsy with and without cataplexy and idiopathic hypersomnia. J. Sleep Res. 11, 91–93.
Krahn, L.E., Pankratz, V.S., Oliver, L., Boeve, B.F., and Silber, M.H. (2002) Hypocretin (orexin) levels in cerebrospinal fluid of patients with narcolepsy: relationship to cataplexy and HLA DQB1*0602 status. Sleep 25, 733–736.
Arii, J., Kanbayashi, T., Tanabe, Y., et al. (2004) CSF hypocretin-1 (orexin-A) levels in childhood narcolepsy and neurologic disorders. Neurology 63, 2440–2442.
Nishino, S., Okura, M., Mignot, E. (2000) Narcolepsy: genetic predisposition and neuropharmacological mechanisms. Sleep Med. Rev. 4, 57–99.
Higuchi, S., Usui, A., Murasaki, M., et al. (2002) Plasma orexin-A is lower in patients with narcolepsy. Neurosci. Lett. 318, 61–64.
Nishijima, T., Sakurai, S., Arihara, Z., and Takahashi, K. (2003) Plasma orexin-A-like immunoreactivity in patients with sleep apnea hypopnea syndrome. Peptides 24, 407–411.
Igarashi, N., Tatsumi, K., Nakamura, A., et al. (2003) Plasma orexin-A levels in obstructive sleep apnea-hypopnea syndrome. Chest 124, 1381–1385.
Bloom, S.R. and Long R.G. (1982) Radioimmunoassay of Gut Regulatory Peptides. Praeger, New York.
Yoshida, Y., Fujiki, N., Maki, R.A., Schwarz, D., and Nishino, S. (2003) Differential kinetics of hypocretins in the cerebrospinal fluid after intracerebroventricular administration in rats. Neurosci. Lett. 346, 182–186.
Lin, L., Wisor, J., Shiba, T., et al. (2002) Measurement of hypocretin/orexin content in the mouse brain using an enzyme immunoassay: the effect of circadian time, age and genetic background. Peptides 23, 2203–2211.
Nishino, S., Mignot, E., Kilduff, T., et al. (1990) Prostaglandin E2 levels in cerebrospinal fluid of normal and narcoleptic dogs. Biol. Psychiatry 28, 904–910.
Yoshida, Y., Fujiki, N., Nakajima, T., et al. (2001) Fluctuation of extracellular hypocretin-1 (orexin A) levels in the rat in relation to the light-dark cycle and sleep-wake activities. Eur. J. Neurosci. 14, 1075–1081.
Nishino, S., Kanbayashi, T., Fujiki, N., et al. (2003) CSF hypocretin levels in Guillain-Barré syndrome and other inflammatory neuropathies. Neurology 61, 823–825.
Harlow, H., and Lane, D. (1998) Using Antibodies: A Laboratory Manual: Portable Protocol No. I. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
Sakurai, S., Nishijima, T., Arihara, Z., and Takahashi, K. (2004) Plasma orexin-A levels in obstructive sleep apnea-hypopnea syndrome. Chest 125, 1963; author reply 1963–1964.
Kanbayashi, T., Inoue, Y., Kawanishi, K., et al. (2003) CSF hypocretin measures in patients with obstructive sleep apnea. J. Sleep Res. 12, 339–341.
Johren, O., Neidert, S.J., Kummer, M., Dendorfer, A., and Dominiak, P. (2001) Prepro-orexin and orexin receptor mRNAs are differentially expressed in peripheral tissues of male and female rats. Endocrinology 142, 3324–3331.
Kirchgessner, A.L., Liu, M. (1999) Orexin synthesis and response in the gut. Neuron 24, 941–951.
Yoshida, Y., Mishima, K., Taheri, S., et al. (2004) Hypocretin immunoreactivity in the blood of genetically engineered narcoleptic mice models. Sleep 27, (suppl.), A247.
Fujiki, N., Yoshida, Y., Ripley, B., Honda, K., Mignot, E., and Nishino, S. (2001) Changes in CSF hypocretin-1 (orexin A) levels in rats across 24 h and in response to food deprivation. Neuroreport 12, 993–997.
Conlon, J.M. (1997) Preparation of neuropeptide-containing fractions from biological materials, in Neuropeptide Protocols (Irvine, C.B., and Williams, C.H., eds.) Humana, Totowa, NJ, pp. 1–16.
Strand, F.L. (1999) Neuropeptides: Regulators of Pysiological Processes. MIT Press, Cambridge, MA.
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Nishino, S. (2006). Hypocretin Measurements in the CSF, and Blood and Brain Tissue. In: Nishino, S., Sakurai, T. (eds) The Orexin/Hypocretin System. Contemporary Clinical Neuroscience. Humana Press. https://doi.org/10.1385/1-59259-950-8:71
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DOI: https://doi.org/10.1385/1-59259-950-8:71
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