Narcolepsy neurons

Thannickal T. C., Moore R. Y., Nienhuis R. et al. (2000). Reduced number of hypocretin neurons in human narcolepsy. Neuron 27, 469-74. 

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... 

Although human narcolepsy is not typically associated with orexin gene mutations, the orexin / model is most similar to the case of a narcoleptic-cataplectic child, severely symptomatic from infancy, who has a genetic defect in orexin production and release (Peyron et al., 2000). Thus, constitutive orexin deficiency alone in the presence of otherwise histologically normal orexin neurons... 

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. 

Hara, J., Beuckmann, C. T., Nambu, T. et al. (2001). Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron 30, 345-54. 

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. 

Willie, J. T., Chemelli, R. M., Sinton, C. M. et at (2003). Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice molecular genetic dissection of Non-REM and REM sleep regulatory processes. Neuron, 38, 715-30. 

Norepinephrine NE transporter Human cDNA Depression, Alzheimer s disease, epilepsy, anxiety, attention deficit hyperactivity, angina, asthma, cardiac arrhythmia, cardiac hypertrophy, congestive heart failure, myocardial ischemia, hypertension, artherosclerosis, narcolepsy, orthostatic hypotension, prostatic hyperplasia, rhinitis, diabetes, diarrhea, glaucoma, impotence, obesity, opiate withdrawal pain, Raynaud s disease, preterm labor pain Modulation of norepinephrine concentration in the neuronal synaptic clefts, neuroprotection... 

Burlet S, Tyler CJ, Leonard CS (2002) Direct and indirect excitation of laterodorsal temental neurons by hypocretin/orexin peptides implications for wakefulness and narcolepsy. J Neurosci 22 2862-72... 

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