A neurotransmitter is a chemical messenger in the brain, transmitting signals between neurons. These messengers coordinate bodily functions, influencing thoughts, feelings, and actions. Orexin, also known as hypocretin, is a neuropeptide. It is produced by specialized neurons located in the hypothalamus, a brain region regulating behaviors like sleep, hunger, and body temperature. Discovered in 1998, orexin influences brain function.
Orexin’s Role in Wakefulness
Orexin plays a role in promoting wakefulness. The neurons that produce orexin project widely throughout the brain, sending excitatory signals to various brain nuclei involved in arousal. These include regions that release neurotransmitters such as dopamine, norepinephrine, histamine, and acetylcholine, which contribute to alertness. By activating these arousal centers, orexin helps to maintain a sustained state of wakefulness and prevents transitions into sleep.
Orexin neurons are highly active during waking hours, releasing orexin-A and orexin-B. This activity helps to ensure that rapid eye movement (REM) sleep, a deep stage of sleep characterized by vivid dreams, does not occur during wakefulness. The interaction between orexin and other neurotransmitters creates a complex system that orchestrates our daily sleep-wake rhythms, promoting alertness and arousal.
When Orexin Production Goes Wrong
A deficiency in orexin production has direct consequences for wakefulness, notably in narcolepsy type 1. This neurological disorder is characterized by the loss of orexin-producing neurons in the hypothalamus. As a result, individuals with narcolepsy type 1 have reduced orexin levels in their cerebrospinal fluid.
This deficiency leads to excessive daytime sleepiness, a hallmark symptom of the disorder, because the brain struggles to maintain alertness. Another common symptom is cataplexy, which involves sudden, brief episodes of muscle weakness or paralysis, often triggered by strong emotions like laughter or anger. Cataplexy occurs because the brain mechanisms that normally cause muscle paralysis during REM sleep become active during wakefulness due to the lack of orexin’s influence on wakefulness.
Orexin’s Broader Influence
While its role in sleep-wake regulation is well-established, orexin also contributes to other bodily functions. It influences appetite regulation by stimulating food intake. Orexin neurons are also linked to reward pathways, impacting motivation and potentially playing a role in addictive behaviors.
Orexin is involved in the body’s response to stress. Orexin-producing neurons respond to environmental pressures by exciting other neurons that increase heart rate and blood pressure, preparing the body for action. This broad influence underscores orexin’s role as a regulator, connecting various physiological processes to arousal and well-being.
Developing Orexin-Targeted Therapies
Understanding orexin’s functions has opened new avenues for therapeutic interventions. For individuals with insomnia, medications known as orexin receptor antagonists have been developed. These “orexin blockers” work by inhibiting the activity of orexin at its receptors, promoting sleep by reducing wakefulness. An example is suvorexant, a dual orexin receptor antagonist.
Conversely, for conditions like narcolepsy type 1, where orexin is deficient, researchers are exploring the development of orexin agonists. These therapies aim to mimic or enhance the effects of natural orexin to promote wakefulness. This dual approach, either blocking or boosting orexin signaling, shows how insights into this neurotransmitter are translated into targeted treatments for sleep disorders and related conditions.