Orexin in the body
Orexin-producing neurons receive signals from the body, emotions, and the environment and then release orexin, which affects the entire central nervous system. In fact, orexins appear to play such diverse roles in the body that researchers believe we are only beginning to understand their importance.
It is believed that orexins are primarily excitatory, meaning they cause other neurons to become active and start sending their own signals. Among the many functions of orexins that have been discovered, they appear to play an important role in sleep, energy metabolism, and mood.
Recent research has proposed a hypothesis that attempts to explain all of orexin's seemingly diverse roles in the body. This hypothesis suggests that orexin regulates behavior during physiological demands, exposure to threats, and opportunities for rewards.
Understanding the multiple roles of orexin in the body is exciting and valuable. Research in this area increases our understanding of the human body. It also offers promising new ways to treat a variety of conditions, including insomnia, narcolepsy, depression, and even obesity.
Sleep and wakefulness
It is hypothesized that orexin's main role is to control sleep and wakefulness, and orexin-releasing neurons are most active during the day. To keep us awake, these neuropeptides stimulate other neurons to release alertness-promoting neurotransmitters such as dopamine, serotonin, and norepinephrine.
Without enough orexin, the body has a hard time staying awake and alert. People diagnosed with narcolepsy type 1 have an 85% to 95% reduction in the number of orexin-producing neurons. Loss of orexin-producing neurons leads to symptoms of narcolepsy, including excessive daytime sleepiness, sleep paralysis, hallucinations, and cataplexy.
Although weight gain is not a symptom of narcolepsy, people with the disorder are more likely to be overweight. Research suggests that the link between narcolepsy and weight gain may be related to the role of orexin in regulating physical activity.
Stress, physical activity and obesity
Orexin is important in the body's response to stress. Orexin-producing neurons receive signals from the environment and respond to stress by stimulating other neurons, which increase heart rate and blood pressure and help the body transition from a resting state to a state where it is ready to react and move.
Because there are fewer chemical signals to trigger a response, orexin deficiency is associated with physical inactivity and obesity. Animal studies show that mice that lose orexin-producing neurons are less physically active, have reduced energy metabolism, and are more likely to suffer from obesity and diabetes, even though they consume fewer calories.
Emotions and Memory
Orexin also excites important neurons that regulate mood. Too much or too little orexin activity has been linked to depression as well as other mental health conditions such as anxiety, panic disorder, addiction and post-traumatic stress disorder.
These neuropeptides also influence mood through their function in the brain's hippocampus. Orexin promotes the production of new neurons in the hippocampus, which is important for learning, memory and spatial abilities. Without enough orexin, people can develop learning and memory problems.
Orexin-targeted sleep aids
Since orexins stimulate wakefulness, blocking the effects of these neuropeptides is one way to treat some sleep disorders. Dual orexin receptor antagonist (DORA) is a new prescription sleep aid that targets the body's orexin system. These drugs work by acting as orexin receptor antagonists, which means they block the effects of orexin in the body, reducing motivation to stay awake and promoting sleep.
Currently, the U.S. Food and Drug Administration (FDA) approves two types of DORA for the treatment of insomnia in adults: suvorexant and lemborexant. The newer DORA is still under development.
DORA is different from other types of sleep aids because they affect different systems in the body. Over-the-counter sleeping pills, such as diphenhydramine and melatonin, can have a sedative effect or help regulate the body's circadian rhythm. Prescription sleep aids promote sleep in other ways, such as by targeting GABA receptors in the brain, but can cause unwanted side effects such as memory problems, behavioral changes, and even hallucinations.
Researchers hope that by targeting the body's orexin system, DORA may be effective and have fewer side effects. In fact, both FDA-approved DORAs have been shown to improve sleep quality in patients with insomnia, and the most common side effect of their use is drowsiness. They also improve sleep architecture and have been used to improve delirium in hospitalized patients.
While DORAs offer a promising new way to treat insomnia, they are not suitable for everyone. Always consult your doctor or sleep specialist before taking any medication. For many people who suffer from insomnia and other sleep problems, it can be helpful to focus on behavioral changes (such as improving sleep hygiene) before considering medication.
