Hypocretins

Orexin A (OX-A) and Orexin-B (OX-B) Hypocretin-1 (Hcttl) and Hypocretin-2 (Hcrt2)... 

Zeitzer JM, Nishino S, Mignot E (2006) The neurobiology of hypocretins (orexins), narcolepsy and related therapeutic interventions. Trends Pharmacol Sci 27 368-74... 

Siegel JM (2004) Hypocretin (orexin) role in normal behavior and neuropathology. Annu Rev Psychol 55 125-148... 

Selbach O, Eriksson KS, Haas HL (2003) Drugs to interfere with orexins (hypocretins). Drug News Perspect 16 669-681... 

Complicated processes govern wakefulness, sleep, and the transitions leading to sleep initiation and maintenance. Although the neurophysiology of sleep is complex, certain neurotransmitters promote sleep and wakefulness in different areas of the central nervous system (CNS). Serotonin is thought to control non-REM sleep, whereas cholinergic and adrenergic transmitters mediate REM sleep. Dopamine, norepinephrine, hypocretin, substance P, and histamine all play a role in wakefulness. Perturbations of various neurotransmitters are responsible for some sleep disorders and explain why various treatment modalities are beneficial. 

Nishino S, Ripley B, Overeem S, et al. Hypocretin (orexin) deficiency in human narcolepsy. Lancet 2000 355 39-40. 

Hypocretin A wakefulness-promoting hypothalamic neuropeptide, a deficiency of which is involved in the pathophysiology of narcolepsy. 

Figure 1.6 (A) Changes in c-Fos IR in hypocretin/orexin(HCRT+)- containing neurons in response to BIC treatment as a function of distance from the microdialysis probe. The percentage of double-labeled cells was greatest closer to the probe (grids 1 and 2, compared with 3 and 4) and was greater with higher concentrations or exposure times. Contralateral cells were not affected. (B) Much lower percentages of melanin-concentrating hormone (MCH+) exhibited c-Fos IR activation in response to BIC. From Alam et al. (2005).

Figure 1.8 Effects of local POA warming on a PLH wake-active, REM-off, putative hypocretin/orexin-containing neuron. POA warming suppressed the waking-related discharge of PLH neurons, in the absence of any state change. The PLH receives strong projections from all subregions of the POA, including GABAergic projections. From Methippara et al. (2003).

Sakurai, T., Nagata, R Yamanaka, A. et al. (2005). Input of orexin/hypocretin neurons revealed by a genetically encoded tracer in mice. Neuron 46, 297-308. 

Bayer, L., Eggermann, E., Saint-Mleux, B. et al. (2002). Selective action of orexin (hypocretin) on nonspecific thalamocortical projection neurons. J. Neurosci. 22, 7835-9. 

Brown, R. E. (2003). Involvement of hypocretins/orexins in sleep disorders and narcolepsy. Drug News Perspect. 16, 75-9. 

Brown, R. E., Sergeeva, O. A., Eriksson, K. S. Haas, H. L. (2002). Convergent excitation of dorsal raphe serotonin neurons by multiple arousal systems (orexin/hypocretin, histamine and noradrenaline). J. Neurosci. 22, 8850-9. 

Eggermann, E Serafin, M., Bayer, L. et al. (2001). Orexins/hypocretins excite basal forebrain cholinergic neurones. Neuroscience 108, 177-81. 

Gerashchenko, D., Salin-Pascual, R. Shiromani, P. J. (2001). Effects of hypocretin-saporin injections into the medial septum on sleep and hippocampal theta. Brain Res. 913, 106-15. 

Lee, M. G., Hassani, O. K. 8r Jones, B. E. (2005). Discharge of identified orexin/ hypocretin neurons across the sleep-waking cycle. J. Neurosci. 25, 6716-20. 

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, 991-7. 

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