Orexin, also known as hypocretin, is a chemical secreted in the hypothalamus that regulates sleep-wake cycle.
Orexin is the name given to a highly excitatory neuropeptide hormone and the two related peptides are orexin A and B.
Narcolepsy is sometimes described as orexin deficiency syndrome.
Orexin A has a greater biological importance than orexin B. Small number of cells produce peptides in the lateral and posterior hypothalamus, but they send projections throughout the brain. The hypocretins are strongly conserved peptides.
Function of orexin:
Initially, the orexin system was suggested to be mainly involved in the stimulation of food intake, based on the finding that central administration of orexin increases food intake.
But, it is discovered that hypocretin dysregulation causes narcolepsy sleep disorder. The discovery indicated that there is a major role of orexin in sleep regulation.
This hormone strongly excites brain neurons with important roles in wakefulness including dopamine, histamine and acetylcholine and plays an important role in stabilizing wakefulness and sleep.
The major role of hypocretin is to integrate metabolic, circadian and sleep debt influences to determine whether the animal should be asleep or awake and active.
Central administration of orexin A promotes wakefulness, increases body temperature and brings a strong increase in energy expenditure.
Orexin A transmission is also increased by sleep deprivation. It is important in the regulation of energy expenditure than food intake. The craving for food is increased by orexin and it correlates with the function of the substances that promote its production.
Leptin acts as a long term internal measure of energy state and ghrelin is a short term factor secreted by the stomach just before an expected meal and strongly promotes food intake.
Hypocretin cells have been inhibited by leptin but are activated by ghrelin and hypoglycemia. Therefore orexin is an important link between metabolism and sleep regulation.
Narcolepsy with orexin deficiency:
Narcolepsy is a condition which results in excessive daytime sleepiness and cataplexy. People lacking hypocretin neuropeptide have narcolepsy.
In narcolepsy patients, hypocretin is missing because of the presence of autoimmune disease. Your body’s immune system, instead of attacking foreign invaders, attack healthy cells and destroys them.
Narcolepsy patients with the deficiency of this hormone have increased obesity rather than decreased body mass index. hypocretin based drugs help narcolepsy patients and increases alertness in the brain without the side effects of amphetamines.
Multiple sleep latencies are significantly shorter in patients with undetectable orexin levels than in patients with detectable orexin levels. The frequency of sleep onset REM periods is higher in patients with undetectable orexin than in patients with detectable orexin.