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The science of sleep: Researchers probe role of neurotransmitter called orexin

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A neurotransmitter discovered in 1998 is getting new attention from scientists. Commonly called orexin, but also known as hypocretin, this family of peptides produced in the hypothalamus portion of the brain is linked to many functions, but is chiefly known for its importance in regulating sleep. In fact, lack of orexin (usually caused by the destruction of the cells that produce this chemical) is the cause of narcolepsy, a sleep-wake regulation disorder.

In a paper published March 21st in the Journal of Neuroinflammation, a team of Australian scientists argue that orexin is a "key regulator" of the biological pathways involved in a variety of functions, including appetite, cognition, motor control, and sleep. In their paper, the researchers describe the activity of the proinflammatory cytokines known as TNF (tumor necrosis factor) and IL-1β (interleukin-1β). These chemicals, produced by the body, are responsible for triggering other internally produced chemicals that provoke an inflammatory response. Thus, TNF and IL-1β have a crucial role in inflammatory diseases such as cancer and rheumatoid arthritis.

In a similar way, orexins (orexin-A and orexin-B, also known as hypocretin-1 and hypocretin-2) have a mediating function on the body's internal chemistry, modulating several different areas of physical responses. Scientists have known for several years that orexin regulates sleep: low levels of orexin induce sleep, and very low levels of orexin can bring about a comatose state. The Australian researchers, Ian Clark and Bryce Vissel, further explain that the body uses sleep as an occasion to "rins[e] the brain of molecules that accumulate while awake." One such molecule is amyloid-beta (Aβ), a substance implicated in the pathology of Alzheimer's disease. The potential clinical importance of such a finding is obvious.

After explicating the possible role of orexin in encephalopathies related to AIDS, traumatic brain injury (TBI), and trypanosomiasis (sleeping sickness), Clark and Vissel discuss the potential for therapies designed to boost orexin activity. One possibility involves deploying an orexin agonist to decrease daytime sleepiness ("sickness behavior") in chronic inflammatory diseases such as type II diabetes. Other potential therapies would depend on synthetic mimics of orexin. It is unclear whether these avenues would be superior to a therapy designed to address the root cause of a particular chronic inflammatory disease.

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