The finding of hypocretin or orexin deficiency in individuals who have narcolepsy indicates that the hypothalamic neuropeptide serves a major function in the regulation and maintenance of sleep or wakeful states along with energy homeostasis.

The hypothalamic neuropeptide may be particularly important for stabilizing behavioral states since the main symptom of narcolepsy is the instability of every behavioral state, resulting in fragmentation of sleep or wakefulness. The afferent and efferent systems of the orexin neurons indicate that there are interactions between the cells and sleep/wakefulness or arousal centers within the brainstem along with essential feeding centers within the hypothalamus.

Overview

Studies show that the regulation of orexin neurons is undertaken by acetylcholine and monoamines along with metabolic cues that include ghrelin, glucose, and leptin. Therefore, orexin neurons consist of the vital functional interactions with cholinergic or monoaminergic centers and hypothalamic feeding paths and provide a crucial link between the core mechanisms that are responsible for coordinating sleep and wakefulness as well as motivated behavior like looking for food and energy balance.

Impact of Orexin Deficiency on Sleep

  • An orexin signaling deficiency leads to a sleep disorder in rodents, dogs, and humans. This disorder features excessive daytime sleepiness and temporary loss of muscle tone or cataplexy.
  • Several approaches that include neuroanatomical, pharmacological, electrophysiological and molecular genetic studies suggest that a critical role is played by orexins in terms of maintaining wakefulness by regulating the function of cholinergic and monoaminergic neurons that are associated with regulating wakefulness.
  • Recent advances have been made in a bid to understand how orexins control sleep and wakefulness and prevent narcolepsy sleep disorder.

Discovering Orexin

Orexin is also referred to as hypocretin, which is a neuropeptide that works by regulating appetite, arousal, and wakefulness. The most prevalent form of narcolepsy that is characterized by cataplexy, results from a lack of orexin inside the brain when the cells that produce it are destructed.

  • The neurons that produce orexin in the human brain are predominantly located in the lateral hypothalamus and perifornical area. These are widely projected within the entire central nervous system to regulate feeding, wakefulness and other types of behavior. Orexin receptors and orexin peptides exist in two forms.
  • Orexin was initially discovered in the late 90s at around the same time by two groups of independent researchers who were observing the rat brain. One of the groups gave it the name ‘orexin’ that is derived from the Greek term for ‘appetite’ while the other group opted to name it ‘hypocretin’ since the hypothalamus produces it and slightly resembles another peptide known as secretin. It is now practically necessary to use both these terms because hypocretin refers to genetic products while orexin refers to protein products. A strong similarity between orexin system within the human brain and rat brain has been observed.
  • In the late 90s, there were reports of the hypocretin or orexin discovery that were published at around the same time. The discovery of hypocretin or the hypocretin system was reported when the discovery or the orexin system was reported to reflect the appetite-stimulating or orexigenic activity of the peptides. Within the paper that described the neuropeptides, the discovery of orexin receptors was also reported.

The two groups of researchers approached their discoveries differently. One team focused on identifying new genes in the hypothalamus with a reported discovery of numerous genes within the rat brain. On the other hand, the other team was interested in studying orexins in terms of being orphan receptors. The naming of the hypocretin and orexin system recognizes the historical background of its discovery.

Function of the Orexin System

The orexin system was first suggested to be mainly involved in stimulating food intake according to the finding that the core administration of A and B caused an increase in food intake. Additionally, it modulates the visceral function, regulates the expenditure of energy and stimulates wakefulness.

Obesity

Among knockout mice, obesity has been attributed to the inability to differentiate brown preadipocytes into brown adipose tissue. Subsequently, this reduces thermogenesis of brown adipose tissue. Restoration of brown adipose tissue differentiation in the mica can be achieved through orexin injections.

Orexin deficiency is also associated with a sleep disorder known as narcolepsy. Additionally, people who are narcoleptic are more likely to be obese. Therefore, obesity in a narcoleptic person may be the result of orexin deficiency that leads to impaired energy expenditure and thermogenesis.

Wakefulness

  • Orexin appears to promote wakefulness. Studies that have been carried out recently show that a crucial role of the system is the integration of sleep debt, circadian and metabolic effects to determine whether animals should be awake and active or asleep.
  • Orexin neurons excite various nuclei of the brain strongly with vital roles in wakefulness that include the acetylcholine, histamine, norepinephrine and dopamine systems and seem to play an essential role in stabilizing sleep and wakefulness.
  • The discovery of a mutated orexin receptor causing the narcolepsy sleep disorder in canines indicated a key role for the system in regulating sleep. The lack of the orexin gene in knockout mice was also linked to narcolepsy. Transitioning rapidly and frequently between wakefulness and sleep among these mice exhibits many of the narcolepsy symptoms. Researchers have used this animal model to study the condition.

Narcolepsy

Narcolepsy leads to cataplexy, a loss of muscle tone when responding to usually positive, strong emotions, inability to consolidate sleep at night and wakefulness during the day and excessive daytime sleepiness. Dogs that do not have a functional orexin receptor have narcolepsy and people and animals that lack the actual orexin neuropeptide also have narcolepsy.

  • Centrally administering orexin A promotes wakefulness strongly, elicits a powerful increase of energy expenditure and increases locomotion and body temperature. Sleep deprivation increases the transmission of orexin A as well. The orexin system may, therefore, be more essential in regulating energy expenditure rather than food intake.
  • Narcoleptic patients who are orexin-deficient have increased obesity instead of decreased BMI, as anticipated of orexin was a peptide that is mainly appetite stimulating.
  • Another indication of orexin deficiency causing narcolepsy is monkeys that are deprived of sleep for several hours and injected with the neurochemical eases the cognitive challenges that are normally witnessed with a large amount of sleep deprivation or loss.

Narcolepsy in humans is linked to a specified human leukocyte antigen complex variant. Additionally, along with the variant, narcoleptic people also showcase a T-cell receptor mutation. In combination, these genetic anomalies result in the immune system attacking and killing the vital orexin neurons. The absence of neurons that produce orexin in narcoleptic people may result from an autoimmune disorder.

Food Intake

Orexin increases food cravings and has a correlation with the function of elements that promote its production. The orexin system is also shown to increase the size of meals due to the suppression of inhibitory post-ingestive response. Some studies, however, suggest that orexin’s stimulatory effects on feeding may be caused by genetic arousal that does not necessarily increase the overall intake of food.

  • Findings indicate that the hyperglycemia that happens in mice because of a high-fat diet, causes a reduction in orexin receptor 2 signaling and orexin receptors might be a therapeutic target in the future. Fat cells produce the leptin hormone that serves as an internal long-term measure of the energy state. The stomach secretes ghrelin as a short-term factor prior to an expected meal and promotes food intake significantly.
  • Recent studies show that the cells that produce orexin have been inhibited by leptin via the receptor pathway and are activated by hypoglycemia and ghrelin.
  • Claims of orexin being an important link between sleep regulation and metabolisms have been made over the years. This relationship has been suspected for a long period of time-based on observations regarding rodents that are sleep deprived on a long-term basis and a dramatic increase in their energy metabolism and food intake and lethal effects in the long run.

Sleep Deprivation and Energy

Sleep deprivation subsequently results in a lack of energy. Many people use high-fat and high-carbohydrate foods to make up for this lack of energy, which can ultimately result in weight gain and poor health.

Amino acids are other dietary nutrients that can activate orexin neurons as well. They can suppress the orexin neurons glucose response at psychological focus, which causes the balance of energy that is maintained by orexin to be thrown off its usual cycle.

Addiction

The first round of research that had been carried out shows orexin blockers can potentially treat alcohol, opioid, and cocaine addiction. For instance, lab rats that have been given drugs that target the orexin system lose interest in alcohol when given unlimited access to it during experiments. There have been mixed results of studies conducted to assess the involvement of orexin in nicotine addiction.

Lipogenesis

  • Orexin A has demonstrated a direct impact on lipid metabolism. Glucose uptake is stimulated in adipocytes and storage of the increased energy uptake is in the form of lipids. Therefore, orexin A increases lipogenesis along with inhibiting lipolysis and stimulating adiponectin secretion. The link between lipid metabolism and orexin A is relatively new and continues to be researched.
  • Obesity in knockout mice is associated with an impairment of thermogenesis.

Mood

High orexin A levels have been linked to happiness in humans while low levels are linked to sadness. Findings suggest that boosting orexin A levels can elevate mood as a possible treatment solution or disorders such as depression.

Clinical Considerations

The hypocretin and orexin system is a target for insomnia medication that functions by blocking the orexin receptors. Clinical trials have been registered for the use of this type of medication for individuals with cocaine dependence.

Increasing Orexin

Orexin or hypocretin controls sleep patterns and may affect your metabolism as well as your ability to lose weight. When your body does not produce a sufficient amount of orexin, you can consider changing your diet by consuming less carbs and sugar, for example. Doctors may recommend medication or supplements as well. It is also advisable to take proper care of your body by losing weight and exercising to naturally increase the orexin levels.

Consuming Fermented Foods

Consuming fermented foods such as pickles and sauerkraut can help to increase the production of orexin. Fermented foods consisting of lactic acid and producing lactic acid can inhibit glucose production, which reduces orexin production. Consuming more fermented foods can be useful for increasing orexin production.

Reducing Carbs and Sugar

When you eat carbs and sugar, your body turns them into glucose. According to research, increasing glucose levels prevents orexin production. Eating less carbs and sugar gives your body an opportunity to produce a higher amount of orexin, which can promote weight loss or increase your energy.

You can minimize carb intake by avoiding starchy foods such as potatoes as well as pasta and bread. Avoid foods that have high sugar content. Several processed foods contain added sugar and it is important to check the nutritional information and facts.

Fasting

Intermittent fasting can increase your levels of orexin. This involves fasting for a substantial number of hours during the day and end the day with a nutritious large meal. If this approach makes you feel worse, resume your normal eating patterns immediately and identify other dietary changes that you can implement to increase the levels of orexin.

Medication

Consult your doctor about medication. If your doctor establishes that you have low orexin levels, certain medications may be prescribed to help your body boost orexin production. If orexin levels are linked to narcolepsy, your doctor may prescribe a controlled substance that you should take responsibility to avoid overdosing.

Orexin A can also be prescribed to increase orexin levels. The drug is administered according to your levels and is usually given in the form of an injection or through the nose. Omega 3 supplements may help to increase levels of orexin in individuals who are not narcoleptic.

Other Options for Increasing Orexin

There are some medically unproven ways to boost orexin levels online but it is advisable to talk to your doctor first before trying anything. Consult your doctor about omega 3 supplements and the appropriate dosage.

Exercise

Increasing your blood acidification can boost your levels of orexin. One of the simple and effective ways to do this is through exercise. Regular exercise is good for overall health and increasing orexin levels.

Weight Loss

Leptin can inhibit orexin production. Since it is produced by fatty tissue in the body, weight loss can reduce the amount of leptin that is produced by the body. Ask your doctor or nutritionist about healthy weight loss techniques. They can inform you about aspects such as different types of exercises and the amount of calories you should consume on a daily basis.

Portion control is one of the best ways to start losing weight. A qualified nutritionist can give you insight into ideal portions and what they should look like. For example, rather than 2 or more servings of each meal, you may be advised to stick to one.

Bright Light

This type of therapy can help to naturally boost orexin production. It involves sitting next to a bright light for a number of hours each day. You may find that you feel less tired. The devices are available online through various retailers.

Monitoring your Sleep Patterns

Everyone is susceptible to feeling tired or worn out from time to time. However, your levels of orexin may be low if you are fatigued or feel sleepy every and occasionally fall asleep during the day. Low levels of orexin can lead to a disorder that is referred to as narcolepsy. See your doctor if you find yourself feeling excessively sleepy during the day.

Appetite

Low levels of orexin can lead to changes in how much you eat your appetite. If you find it hard to control the amount of food you eat or feel hungry all the time, your orexin levels may be the culprit.

Libido

Another sign of low levels of orexin is lack of sexual interest or low libido. If you notice a drastic change that affects your sex drive, your levels of orexin may have dropped.

Fidgeting

Fidgeting a lot may be another symptom of low levels of orexin. You can ask someone else to keep track of how often you fidget since you may not always notice when you do it.

Aspects of Narcolepsy

Narcolepsy is a type of sleep disorder that is characterized by hallucinations. sleep paralysis, excessive sleepiness and cataplexy (total or partial loss of muscle control that is usually triggered by strong emotions like laughter) in some cases.

  • People who have narcolepsy feel extremely sleepy during the day and are likely to fall asleep involuntarily during normal activities. The typical boundary between being asleep and awake is blurred in narcolepsy. This means that the characteristics of sleep may occur when the individual is awake. For instance, cataplexy consists of the muscle paralysis that occurs in REM sleep during waking hours. Cataplexy causes loss of muscle tone that results in weakness of the trunk, legs or arms or a slack jaw. People who have narcolepsy may also experience paralysis and hallucinations while waking up or falling asleep as well as vivid nightmares and disrupted sleep at night.
  • Narcolepsy that is characterized by cataplexy results from a loss of chemical in the brain that is called orexin or hypocretin. This chemical acts on the alert systems of the brain to regulate the sleep-wake cycle and keep people awake. With narcolepsy, the cells that are responsible for producing hypocretin (located in the hypothalamus region) are completely destroyed or damaged.
  • People find it difficult to stay awake without hypocretin and may also experience a disrupted sleep-wake cycle. While there is no actual cure for the condition, behavioral treatments and medications can help to ease the symptoms for individuals in order for them to be able to lead productive, normal lives.
  • Narcolepsy can be diagnosed through a physical examination, conducting sleep studies and taking the person’s medical history. If you have narcolepsy, the combination of behavioral changes and medication is considered to be the most effective treatment.

Support Groups

People who have been diagnosed with the condition are advised to seek counseling through support groups and educational networks. Getting a narcolepsy diagnosis and dealing with the symptoms can be challenging and the general public does not fully understand the disorder. It is always helpful to access support from other people who have the disorder and become familiar with the best practices.

Sleep-Wake Cycle

  • Narcolepsy is the numerological disorder that affects how sleep and wakefulness are controlled. Individuals with narcolepsy experience uncontrollable, intermittent, episodes of sleeping during the daytime and excessive daytime sleepiness. The sudden attacks of sleep may happen during any kind of activity and at any time of the day.
  • Within a normal sleep cycle, we begin by entering the early sleep stages that are followed by deeper stages of sleep and ultimately REM or rapid eye movement sleep. For people who suffer from the disorder, REM sleep happens almost immediately within the sleep cycle and periodically during waking hours as well.
  • In REM sleep we can experience muscle paralysis and dreams, which gives insight into the symptoms of narcolepsy. The condition can become apparent at virtually any age and in cases where it is not diagnosed, it remains untreated.

Causes of Narcolepsy

Scientists have made significant progress towards finding out the genes that are strongly linked to the disorder. The genes control chemical production in the brain that affects sleep-wake cycles. Many experts consider narcolepsy as the result of a deficiency in the production of hypocretin or orexin by the brain.

Additionally, researchers have found abnormalities in the different parts of the brain that are involved in controlling REM sleep. The abnormalities may contribute to the development of symptoms. Experts believe that narcolepsy consists of numerous factors that interact and cause REM sleep disruptions and neurological dysfunction.

Symptoms

Narcolepsy symptoms include the following:

  • Excessive daytime sleepiness- Generally, excessive daytime sleepiness disrupts normal activities every day regardless of whether or not the individual with narcolepsy had enough sleep at night. Individuals with excessive daytime sleepiness often report extreme exhaustion, depressed mood, memory lapses, lack of concentration and energy or mental cloudiness.
  • Cataplexy- This typically involves a loss of muscle tone that causes feelings of weakness along with losing voluntary muscle control. It may lead to symptoms that range from complete body collapse to slurred speech, depending on the muscles that are involved. It is usually triggered by an intense emotion like anger, laughter or surprise.
  • Hallucinations- Delusional experiences are usually frightening and vivid. The content is mainly visual but the other senses may also be involved. Hallucinations may accompany the onset of sleep or occur when waking up.
  • Sleep paralysis- This consists of the brief inability to speak or move while waking up or falling asleep. These episodes are typically temporary and may last for several minutes or a few seconds. People recover rapidly after the episodes end and have the full capacity to speak and move.

Diagnosis

An exhaustive medical history and physical exam are crucial for properly diagnosing narcolepsy. However, it is important to note that none of the symptoms are exclusive to the disorder. Many specialized tests that can be carried out in a sleep lab or clinic are usually required before establishing a diagnosis.

Treatment

  • The major disabling symptoms of narcolepsy such as cataplexy and excessive daytime sleepiness can be regulated in people through drug treatment. Amphetamine stimulants may be used to treat sleepiness while antidepressants can be considered for abnormal REM sleep.
  • Medication that has been approved for narcolepsy that features cataplexy is aimed at helping people get a better night of sleep and enable them to be less sleepy in the daytime. Medical treatment may not completely cure narcolepsy but it provides substantial help for patients.
  • Lifestyle changes such as avoiding heavy meals, nicotine, alcohol, and caffeine, establishing a meal and exercise schedule, scheduling daytime naps and regulating a sleep schedule can help to minimize the symptoms.

Who is affected by Narcolepsy?

Narcolepsy that is linked to orexin deficiency is regarded as a relative rate condition. It is not easy to know the exact number or percentage of people who have narcolepsy because several cases are not reported. However, estimates show that a significant number of people are affected.

Men and women are equally affected by the disorder although there are some studies that indicate the condition may be more prevalent among men. Symptoms may start to appear during adolescence but the condition is typically diagnosed from the age 0f 20.

Managing the Symptoms of a Sleep Disorder

With more research showing how lack of orexin can affect have an adverse effect on the sleep-wake cycle, it is important to be able to deal with the sleep disorder effectively and improve the overall quality of life. Narcolepsy is characterized by a lower quality of sleep and a disrupted sleep pattern.

Individuals who suffer from the condition may experience brief muscle paralysis that is commonly referred to as cataplexy, vivid dreams, sudden weakness, and daytime sleepiness. The disorder cannot be cured but certain lifestyle changes and medications can effectively manage the symptoms.

Identifying the Causes

One of the important steps towards living a productive and normal life despite having a sleep disorder is to understand what may be causing it. Various things can trigger or cause narcolepsy. Identifying the underlying problem can make it easier for you to manage the symptoms.

For several people, lack of orexin (hypocretin) in the body causes narcolepsy. This may be the result of an autoimmune response or a genetic problem. With an autoimmune response, the body attacks parts of the body where orexin is produced. You might be able to increase orexin or hypocretin in your body.

Improving Sleeping Habits

Since there is no clear cure for this particular type of sleep disorder, patients are assured that they can ease the symptoms by managing their individuals sleeping schedules better. Make an effort to develop healthy sleeping habits to minimize the sudden muscle collapse and excessive daytime sleepiness that is associated with narcolepsy.

Creating a Comfortable Environment

Having a comfortable environment within your bedroom or sleeping area can be useful for promoting restful sleep. You can make a few alterations to your room to improve your sleep.

  • Ensure that your pillows and mattress are comfortable and supportive. If you wake up consistently with a sore back or sore neck, you may need to replace your mattress or pillow.
  • Make sure that all your bed supplies and linen are hypoallergenic to avoid disrupted sleep.
  • Try to create a clear boundary between sleep and wakefulness. Phones, televisions, and laptops should ideally be kept out of the sleeping area. If you reside in a noisy area, there are various ways and devices you can use to block out unwanted sounds.
  • Keep your room cool or maintain a temperature that you are comfortable with.
  • You can install curtains if too much light comes through your window. Good curtains are useful if you are in a location that experiences long summer days or there are bright street lights outside. Stress can worsen the symptoms of a sleep disorder.

Relieving Stress

Making an effort to control your stress levels can help to reduce the symptoms. There are various activities that you can get involved in to reduce stress.

  • Breathing exercises- There are a number of breathing exercises that aim to slow down the heart rate and help to ease the physical symptoms of high-stress levels.
  • Meditate- Meditating reduces stress by keeping your thoughts within the present moment. Meditation on a daily basis can ease the symptoms of a sleep disorder.
  • Yoga- This gets all our body parts to work together along with being a great way to clear your mind. It has the additional benefit of being a type of exercise that can regulate your sleeping schedule.

Therapy and Medical Intervention

Any type of chronic condition can be hard to manage. People who suffer from hormone imbalances and sleep disorders may develop psychiatric issues such as anxiety and depression as a result of the condition. Consulting a therapist can be helpful in the management of the emotional effects of a sleep disorder. Physical aspects of the condition can be handled by a qualified physician.

Boosting Orexin

Lack of orexin has been linked to narcolepsy in many cases. You might be able to boost orexin production naturally by reducing inflammation within your body, eating a healthy diet and exercising on a regular basis. Some of the ways to increase the chemical production in your body include going outside, identifying the food allergies that might cause inflammation, consuming fermented food and bright light therapy.

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