What is Noradrenaline? | Mental Health America

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Noradrenaline (also called “norepinephrine”) is a chemical created in your nerve endings that helps you stay focused and alert. With noradrenaline, you want a “Goldilocks” amount that’s just enough to keep you going. Too much can cause anxiety while too little brings on symptoms of depression. Keep reading to learn everything you need to know about this important neurotransmitter, what medications can help you control it, and how you can maintain your noradrenaline balance naturally.

What is noradrenaline?

Noradrenaline is a neurotransmitter created in your brain stem.^[1] A neurotransmitter sends a message from one neuron to another. Once it sends its message, its work is done and it’s reabsorbed by your body. For noradrenaline, in particular, you might think of that message as saying, “Wake up!”^[2]

• Noradrenaline is mainly a neurotransmitter, but it’s also a hormone. Hormones send messages too, but they travel through the bloodstream instead of across neural pathways.
• Unlike neurotransmitters, hormones aren’t reabsorbed—they keep traveling through the bloodstream and communicating their message throughout your body.^[3]

What is the difference between noradrenaline and adrenaline?

Noradrenaline is a neurotransmitter and adrenaline is not. The hormones adrenaline and noradrenaline are produced in your adrenal glands. However, your brain stem also produces noradrenaline as a neurotransmitter. Both hormones and neurotransmitters carry messages from one part of your body to another, but hormones have a much broader range than neurotransmitters do.^[4]

• Neurotransmitters tend to have very short-lived effects, while hormones act over a longer period. But since noradrenaline is both, it’s capable of affecting your body and behavior in both the short and the long term.

Noradrenaline is released all the time, not just when danger is present. When your brain senses danger, it triggers a flood of adrenaline into your bloodstream to help you combat or escape that danger—the so-called “fight or flight” response. Noradrenaline is released then too, but it’s also released normally throughout the day whenever you need to be more alert.^[5]

• For example, if you’re lounging on the couch watching TV and get up to get a snack, you’ll get a small push of noradrenaline to get you moving.
• Noradrenaline production slows at night when you lie down to go to bed, but if you stand up and start moving around, you’re likely to get a quick burst of noradrenaline. This is why it’s so hard to “stay sleepy” if you get up to go to the bathroom in the middle of the night.

What Noradrenaline Does

Increases your heart rate. The neurotransmitter works with adrenaline to speed up your heart at signs of danger, which also increases the amount of blood pumping from your heart. It also constricts your blood vessels to increase your blood pressure. If your life is threatened, this gives you more strength to overcome the danger.^[6]

Gives you more energy. Noradrenaline breaks down fat and increases your blood sugar levels to give you that extra burst of energy to get going. When you’re facing danger, this helps you fight or flee. But noradrenaline carries on this role to a lesser extent even when you’re not in danger.^[7]

• For example, when you wake up in the morning, your brain sends a small burst of noradrenaline into your bloodstream to help get you going.
• When you’re exercising, it’s noradrenaline that helps you power through a tough part of your workout. If you’ve ever had a moment where you felt like you were wiped out, then got a sudden burst of energy, that was noradrenaline.^[8]

Maintains your metabolism and biorhythms.  Most of the functions of your body occur on cycles, and noradrenaline plays a role in keeping these rhythms steady so your body continues to function normally. These cycles are disrupted without sufficient noradrenaline.^[9]

• For example, noradrenaline helps maintain your circadian rhythm. If your sleep cycle gets out of whack—say, you pull an all-nighter—you might end up with too much noradrenaline in your system, which can leave you jittery and anxious.

Ensure proper organ function. Noradrenaline helps trigger smooth muscle—that’s the muscle that makes up your internal organs—to move and react to change. This keeps your organs functioning normally to keep your body healthy.^[10]

• For example, after you eat a meal, noradrenaline signals your stomach and intestines to start the digestion process.

How Noradrenaline Affects Everyday Functioning

Noradrenaline wakes you up and gets you moving.  Your body pumps out noradrenaline throughout the day, but that production slows down during the evening as you get ready to go to sleep. Production is lowest at night, then jumps back up again in the morning.^[11]

• The extra noradrenaline in the morning is one of the reasons it’s usually best to tackle your most difficult tasks first—you’ll be better able to give them the attention they deserve.

Noradrenaline helps you pay attention and learn. Small bursts of the neurotransmitter send messages through your nervous system to keep you alert and attentive. By helping to hold things in your working memory, noradrenaline helps you remember things that you’ve learned—rather than those things going in one ear and out the other.^[12]

• If you’ve ever felt yourself drifting off and then suddenly snapped to attention, you likely got a short burst of noradrenaline.

Noradrenaline’s Role in Mental Health

Too much noradrenaline causes anxiety, irritability, and difficulty sleeping.  Noradrenaline causes you to feel awake, but you don’t need to be awake all the time, right? High levels of noradrenaline result in high levels of alertness, which are really taxing to you mentally and physically.^[13]

• Panic attacks can be caused by too much noradrenaline. Likewise, if you have a hard time falling asleep or staying asleep, too much noradrenaline might be to blame.
• With too much noradrenaline, you typically feel as though you’re always on edge. Since your senses are heightened to some degree, lights seem brighter and noises seem louder. All of this can make you extremely irritable.

Too little noradrenaline leads to depression, poor memory, and a lack of energy. Remember that burst of noradrenaline that helps you get out of bed in the morning? If you don’t ever get it, you might not feel like getting out of bed at all. Feeling lethargic and unmotivated are often signs of low levels of noradrenaline—as well as major symptoms of depression. ^[14]

• ADHD is also associated with low noradrenaline levels, which cause difficulty with focus and concentration.

Controlling Noradrenaline with Medication

Psychostimulant medications increase noradrenaline for people with ADHD. The most common medications for ADHD increase both noradrenaline and dopamine. These include methylphenidate (Ritalin/Concerta), dextroamphetamine (Dexedrine), and Adderall.^[15]

• Atomoxetine (Strattera) is a drug developed specifically for ADHD and only affects noradrenaline. It has less potential for abuse than psychostimulants but research shows it might not be as effective in treating ADHD.

Serotonin-norepinephrine reuptake inhibitors (SNRIs) treat depression. These drugs work by keeping noradrenaline from being re-absorbed and stored in nerve endings. This results in more noradrenaline in your body.^[16]

• SNRIs include duloxetine (Cymbalta, Yentreve) and venlafaxine (Effexor).
• Some people respond better to SNRIs than they do SSRIs (selective serotonin reuptake inhibitors), such as fluoxetine (Prozac). SSRIs are the most commonly prescribed antidepressant and don’t affect noradrenaline.^[17]

Tricyclic antidepressants (TCAs) also increase noradrenaline. These older drugs have a lot of side effects that people don’t like, including dry mouth, constipation, and weight gain. Because of this, they’ve been largely replaced by newer drugs with fewer side effects.^[18]

• Your doctor might prescribe a TCA if you’ve tried other drugs and they haven’t helped manage your depression. Common TCAs include amitriptyline (Elavil), clomipramine (Anafranil), dosulepin, imipramine (Tofranil), lofepramine, and nortriptyline (Pamelor).^[19]

Work with your doctor to find the right medication.Mental health conditions typically involve more than one neurotransmitter and finding the best medication can be tricky. It’s totally normal to try several different medications before you land on the one that treats your symptoms with minimal side effects.^[20]

• Your doctor will want to know how long you’ve been having your symptoms as well as what you’ve done to cope with those symptoms.
• If you’ve taken any supplements to treat your symptoms, let your doctor know about those as well. Your body’s response to those supplements might help your doctor determine what medication to prescribe.

Ways to Naturally Correct Noradrenaline Imbalance

Exercise for 20-30 minutes a day to regulate noradrenaline levels. Routine exercise helps stabilize your noradrenaline levels over time. In fact, routine exercise can be just as effective as antidepressants in treating anxiety and depression, as long as you stay consistent.^[21]

• If you have depression, it can be difficult to motivate yourself to exercise every day. This is one of the many reasons taking antidepressant drugs can be so helpful.
• Once you develop a consistent exercise routine, you might find that you can decrease your dose or even stop taking antidepressants altogether.
• If you have an anxiety or panic disorder associated with too much noradrenaline, regular exercise can help lower your noradrenaline levels. This happens because physical activity mimics the fight-or-flight response—it’s just that instead of running from a bear, you’re just running (or walking, or swimming, or even dancing).

Combine exercise with relaxation techniques to further reduce noradrenaline. A therapist can help you discover the relaxation techniques that work best for you. Deep-breathing exercises and meditation are two clinically proven ways to lower noradrenaline and calm your body and mind.^[22]

• Grounding is one simple exercise you can try if you’re feeling anxious or overwhelmed. Start by focusing on your breath. As you take slow, deep breaths, start by naming 5 things you see around you. Then, name 4 things around you that you can touch. Name 3 things around you that you can hear, followed by 2 things around you that you can smell. End the grounding exercise by naming 1 thing around you that you can taste.^[23]

Boost serotonin and dopamine through small accomplishments. Serotonin and dopamine work together to make you feel better about yourself and your life—and the good news is that every little accomplishment gives you a little hit of these happy chemicals. Since dopamine helps make noradrenaline, making more dopamine means more noradrenaline as well.^[24]

• Keep a “to do” list to give yourself little bursts throughout your day. No accomplishment is too small not to be included on your list! There’s no shame in including “get out of bed” as an accomplishment in and of itself.
• Divide large tasks into smaller ones so you have more accomplishments to celebrate. For example, if you have an essay due for a class, you might consider each paragraph a separate accomplishment.

Take amino acid supplements to boost noradrenaline levels. Your body makes noradrenaline from dopamine, so you have to start there. Your body synthesizes dopamine from the amino acids tyrosine and phenylalanine, which you can buy in supplement form.^[25] A healthy adult needs 25 milligrams (0.00088 oz) of these amino acids per 1 kilogram (2.2 lb) of body weight.^[26]

• You can also get these amino acids in the foods you eat. Foods high in tyrosine include dairy products, meat, poultry, fish, beans, soybeans, and whole grains.^[27]
• Phenylalanine also makes tyrosine. Foods high in phenylalanine include meat and meat products, dairy products, and whole grains. ^[28]

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Sources

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2. https://qbi.uq.edu.au/brain/brain-physiology/what-are-neurotransmitters
3. https://medlineplus.gov/hormones.html
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5. https://www.yourhormones.info/hormones/adrenaline/
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7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548657/
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9. https://www.ncbi.nlm.nih.gov/books/NBK540977/

10. https://onlinelibrary.wiley.com/doi/10.1002/cphy.c140007
11. https://www.ncbi.nlm.nih.gov/books/NBK540977/
12. https://www.ncbi.nlm.nih.gov/books/NBK540977/
13. https://universityhealthnews.com/daily/depression/surprising-research-challenges-our-understanding-of-norepinephrine-deficiency/
14. https://onlinelibrary. wiley.com/doi/full/10.1002/da.20642
15. https://www.caam.rice.edu/~cox/wrap/norepinephrine.pdf
16. https://www.caam.rice.edu/~cox/wrap/norepinephrine.pdf
17. https://www.nhs.uk/mental-health/talking-therapies-medicine-treatments/medicines-and-psychiatry/antidepressants/overview/
18. https://www.caam.rice.edu/~cox/wrap/norepinephrine.pdf
19. https://www.nhs.uk/mental-health/talking-therapies-medicine-treatments/medicines-and-psychiatry/antidepressants/overview/
20. https://familydoctor.org/how-to-safely-take-antidepressants/
21. https://www.apa.org/topics/exercise-fitness/stress
22. https://www.apa.org/topics/exercise-fitness/stress
23. https://www.urmc.rochester.edu/behavioral-health-partners/bhp-blog/april-2018/5-4-3-2-1-coping-technique-for-anxiety.aspx
24. https://www.psychologytoday.com/us/blog/the-truisms-wellness/201610/the-science-accomplishing-your-goals
25. https://universityhealthnews.com/daily/depression/surprising-research-challenges-our-understanding-of-norepinephrine-deficiency/
26. http://apps. who.int/iris/bitstream/handle/10665/43411/WHO_TRS_935_eng.pdf;jsessionid=1A595365E103CF4CD033278E0749E1F7?sequence=1
27. https://link.springer.com/article/10.1007/s00426-017-0957-4
28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315330/

Factors that Increase Norepinephrine + Deficiency Symptoms

Your body has powerful systems in place to make sure norepinephrine levels remain in a healthy range, but sometimes things go wrong. Read on to learn how the balance can be upset, and what factors might help restore it.

What Is Norepinephrine?

You may have just landed here from one of our previous articles on the function and effects of norepinephrine. If so, then you know that norepinephrine is a catecholamine neurotransmitter involved in the fight or flight response. If not, you may want to brush up on the basics of norepinephrine before you read on.

Norepinephrine Deficiency

The causes and conditions shown here are commonly associated with low norepinephrine. Work with your doctor or other health care professional for an accurate diagnosis and appropriate treatment or management plan.

DBH Deficiency

The leading cause of norepinephrine deficiency is a genetic disorder called dopamine beta hydroxylase (DBH) deficiency. At least six variations in the DBH gene can cause this disorder, with the most common being the C allele at rs74853476 [1, 2, 3].

Dysfunctional DBH causes norepinephrine deficiency because this enzyme converts dopamine into norepinephrine. A person must have two abnormal versions of DBH to be genetically deficient in norepinephrine [1, 2, 3].

People with DBH deficiency may be prescribed droxidopa to manage their blood pressure. Droxidopa is converted to norepinephrine not by DBH, but by another enzyme called L-aromatic amino acid decarboxylase [4].

Symptoms of DBH Deficiency

People with DBH deficiency have difficulty regulating their body temperature and blood pressure. The condition is often discovered in late childhood as symptoms develop: vomiting, dehydration, low blood pressure, and low blood sugar are common [5].

Low blood pressure has its own complications, among them dizziness, blurred vision, and difficulty exercising. Some people with DBH deficiency may have more severe symptoms, including [5]:

• High palate
• Low blood sugar at birth
• Frequently waking at night to urinate
• Sudden drops in blood pressure when standing up
• Drooping eyelids
• Retrograde ejaculation, which may lead to infertility [6]
• Seizures, possibly due to a lowered seizure threshold [7]
• High insulin levels and insulin resistance [8]

People with DBH deficiency have, on average, smaller brain volume than the average population. Fortunately, however, their brain function is largely intact, with no evidence of cognitive delay. Some researchers speculate that other neurotransmitters, such as dopamine, take over the function of norepinephrine in this population [9].

Congenital Insensitivity to Pain with Anhidrosis

It’s a mouthful: congenital insensitivity to pain with anhidrosis, or CIPA, is a condition marked by the inability to feel pain or to sweat. Norepinephrine is not part of the diagnostic criteria of the disease; however, children with CIPA have extremely low – sometimes completely undetectable – levels of norepinephrine [10, 11].

Drugs that Reduce Norepinephrine

Some medications reduce blood pressure and decrease norepinephrine. These include clonidine, prazosin, terazosin, atenolol, metoprolol, and propranolol. Reducing norepinephrine is usually the intended result of taking these drugs; however, if the dosage is too high, this neurotransmitter (and, thus, blood pressure) can be lowered to a dangerous degree [12, 13, 14].

Possible Consequences of Low Norepinephrine

Norepinephrine has many crucial effects in the brain and body. Deficiency might affect its ability to perform any of its functions listed below, but this should not be considered an exhaustive list of symptoms produced or processes disrupted by a dysfunctional norepinephrine system.

1) Mood Disruption

We’re always looking for benefits that don’t need a lab test—benefits that we can really feel in our daily lives—and here’s one! Norepinephrine can regulate emotions, fight depression, and improve mood.

Norepinephrine increases vigilance, arousal, attention, motivation, reward, learning, and memory [15].

Catecholamines and Depression

Catecholamines have been implicated in depression since the 1960s. At the time, the “catecholamine hypothesis of affective disorders” was highly controversial.

Researchers have since developed many hypotheses about brain chemistry and depression; however, it is broadly accepted that people with low catecholamines, including dopamine and norepinephrine, are more likely to be depressed [16, 17, 18, 19, 20].

During depression, serotonin (5-HT) and norepinephrine (NE) neurotransmission are usually significantly lower than normal [21, 22].

That’s why some of the most common antidepressant medications are serotonin and norepinephrine reuptake inhibitors, or SNRIs. These medications stop serotonin and norepinephrine from re-entering the neuron, leaving more of them available and effective for longer [21, 22].

According to some researchers, these SNRIs may be more effective antidepressants than the selective serotonin reuptake inhibitors, or SSRIs [23].

2) Memory and Cognitive Function

Norepinephrine released by the locus coeruleus affects brain function in a number of ways.

It enhances sensory processing, attention, and the formation and retrieval of both long-term and working memory. Norepinephrine is necessary for access to a memory and is important for consolidation and retrieval of some types of memory [24, 25, 26].

Alzheimer’s Disease

Some researchers believe that a lack of this neurotransmitter may underpin some of the effects of cognitive aging. Loss of norepinephrine neurons in the locus coeruleus of the brainstem occurs in Alzheimer’s disease [27, 28].

Norepinephrine slows or even reverses neurodegeneration in animal models, raising the possibility that increasing it may have a role in the development of Alzheimer’s [29, 30].

Parkinson’s Disease

Norepinephrine is also decreased in Parkinson’s disease. In several regions of the brain, it’s reduced to less than half of its usual tissue concentration [31, 32].

According to some researchers, loss of norepinephrine function may partially cause, or at least worsen, Parkinson’s disease. Activity in the locus coeruleus—which is full of norepinephrine—may stimulate and protect the substantia nigra, the part of the basal ganglia that deteriorates during Parkinson’s. If the locus coeruleus fires at a decreased rate, the substantia nigra may become more sensitive to toxic agents and die off more quickly [33, 34].

One of the earliest signs of Parkinson’s disease is decreased attention and focus. This, along with the decreased activity of the locus coeruleus, implicates norepinephrine in the development of this disease [34].

Because the attentional symptoms precede the motor symptoms of Parkinson’s, some researchers are investigating norepinephrine as an early intervention [35].

3) ADHD

Of course, if we’re going to talk about decreased attention and focus, we have to address ADHD. Norepinephrine increases alertness and lets us “dial in” to a task, challenge, or threat. In people with attention deficit hyperactivity disorder, the aforementioned ADHD, norepinephrine function is in disarray [36].

People with ADHD have irregular (but usually low) norepinephrine transmission to the α1 and α2 adrenoreceptors. In the healthy brain, norepinephrine regulates the “switch” between focus and flexibility. In the ADHD brain, this switch appears to be poorly regulated; people with ADHD are usually distractible, with periods of intense “hyperfocus” in between [37, 38, 39, 40].

Drugs that increase norepinephrine have been effective in treating ADHD. Specific norepinephrine reuptake inhibitors are a non-stimulant option in the treatment of ADHD [41, 42].

4) Chronic Fatigue Syndrome and Fibromyalgia

Chronic fatigue syndrome, or CFS, is a debilitating condition marked by long stretches of exhaustion with no obvious cause. According to one study, people with CFS did not have a healthy response to physical exercise or exertion: where the average person’s norepinephrine levels would rise, theirs stayed low [43].

Fibromyalgia seems to be closely related to CFS; however, people with CFS have more fatigue, and people with fibromyalgia have more pain. Some people may suffer both conditions at once [44, 45].

The role of norepinephrine in CFS and fibromyalgia is unclear. While it appears to stay low during exercise, medications that increase norepinephrine may not be helpful.

Serotonin and norepinephrine reuptake inhibitors (SNRIs) like duloxetine do not improve symptoms of CFS. These medications have likewise had mixed results in fibromyalgia, with improvements in only a few patients [46, 47].

To further complicate things, a study of teenagers with CFS actually found that they had a higher baseline level of norepinephrine. These results have led some researchers to suggest that the system controlling norepinephrine response could be dysfunctional in people with CFS [48].

5) Bipolar Disorder

Bipolar disorder is a condition that causes swings or “switches” between manic and depressive episodes. People with bipolar disorder may have weeks or months of high energy, productivity, and good mood… followed by weeks or months of deep depression [49].

The exact cause of bipolar disorder is unknown, but people with the condition have lower levels of norepinephrine. Furthermore, antidepressants that increase norepinephrine have been successful treatment options [50].

Bupropion, which increases both norepinephrine and dopamine, has been among the more effective antidepressants for people with bipolar disorder. It is also associated with a low frequency of switching between manic and depressive states [51, 52].

Interestingly, bupropion has better treatment outcomes than serotonin norepinephrine reuptake inhibitors (SNRIs). Plus, drugs that only affect norepinephrine have been linked to more frequent mild to moderate manic episodes [51, 53].

Bipolar disorder is poorly understood. Researchers are still figuring out what causes it, how it progresses, and whether norepinephrine could be at the root.

6) Migraines

Some studies suggest that people with debilitating migraine headaches may have an imbalance of norepinephrine compared with other neurotransmitters. When a migraine begins, sufferers tend to have relatively low norepinephrine and relatively high dopamine, prostaglandins, adenosine triphosphate, and adenosine [54, 55].

An enzyme called dopamine beta hydroxylase, or DBH, is responsible for converting dopamine into norepinephrine. Low levels or dysfunction of this enzyme could increase dopamine and decrease norepinephrine. This, in turn, could cause an imbalance of neurotransmitters. Some researchers have suggested this as a potential mechanism for migraine, though it has not been directly observed in people [55].

Serotonin and norepinephrine reuptake inhibitors, or SNRIs, are often used to prevent migraine. They have generally been more effective than selective serotonin reuptake inhibitors (SSRIs), a point in favor of the idea that they could work by restoring the balance between norepinephrine and dopamine [56].

7) Metabolism and Weight

Increased norepinephrine has been linked to weight loss. In obese mice, intermittent fasting increased both norepinephrine and the rate of fat loss; however, it is unclear whether norepinephrine promoted weight loss in these animals [57].

By contrast, high levels of norepinephrine in the blood seem to predict future weight increase in people who are trying to maintain their weight [58].

Future research will clarify the role of norepinephrine in metabolism and weight management.

Factors that May Increase Norepinephrine

Most importantly, work with your doctor to treat any underlying conditions causing low norepinephrine levels. You may try the additional strategies listed below if you and your doctor determine that they could be appropriate and will not interfere with existing therapies. None of these strategies should ever be done in place of what your doctor recommends or prescribes.

Your Favorite Things

Obviously, one shouldn’t seek out stressful experiences just to increase norepinephrine. The good news is: you don’t have to!

According to a rat study, norepinephrine increases in response to strong stimuli, both positive and negative. Animal and human studies have confirmed that powerful emotions of all kinds can trigger norepinephrine release. That means that any experience that makes you feel strongly (and requires a lot of brain power to process) may increase norepinephrine [59, 60].

Foods and Diet

Caffeine triggers the release of norepinephrine from the locus coeruleus. Foods containing caffeine—coffee, chocolate, soda, energy drinks—may, therefore, increase norepinephrine levels. However, green tea, which contains caffeine, did not increase norepinephrine in healthy volunteers. The authors suggested that this may be because green tea contains other compounds that counteract some of caffeine’s effects [61, 62, 63].

Meat, fish, eggs, cheese, and nuts are all high in protein and, thus, high in phenylalanine and tyrosine, the precursors to norepinephrine. However, it is unlikely that eating more of these amino acids could increase norepinephrine in people who are not deficient [64, 65, 66, 67].

Decreasing salt intake may also increase norepinephrine under certain circumstances. In a study of people with high blood pressure, a low sodium diet significantly increased norepinephrine in the blood [68].

Exercise

Over a period of several days, exercise increases norepinephrine turnover in humans. In mice, exercise reduced the number of norepinephrine transporters in the brain, which allows more of this neurotransmitter to stay outside the neurons [69, 70].

In this way, exercise acts as a norepinephrine reuptake inhibitor – but not right away. If you want to use exercise to increase norepinephrine, you’ll need to stick to your fitness plan for days, weeks, and months at a time [70].

Exercise and cold temperatures have both been found to increase norepinephrine turnover: that is, the rate at which the sympathetic nervous system releases and uses norepinephrine. In rats, cold exposure also decreases norepinephrine reuptake after the event, which may leave more of this neurotransmitter available in the blood in the longer term [69, 71, 72].

Supplements that May Increase Norepinephrine

Norepinephrine itself is currently only available by prescription as a drug called levophed. We strongly recommend against taking levophed without a doctor’s prescription [73].

Some other supplements have produced increases in norepinephrine in small clinical trials. However, not enough evidence is available to recommend these for the purposes of increasing norepinephrine. Talk to your doctor about the possible underlying causes of and strategies to manage low norepinephrine.

Herbal Supplements

At least one commercial weight loss supplement – a combination of yohimbine, caffeine, and synephrine – has been found to increase norepinephrine in two small clinical trials of healthy men. Yohimbine alone also increased norepinephrine in the blood of 23 healthy adults [74, 75, 76].

A combination of caffeine and bitter orange also increased norepinephrine in a small clinical study of 14 volunteers [77].

Norepinephrine Precursors

Norepinephrine biosynthesis starts with either of two amino acids: phenylalanine and tyrosine. Note that some research contradicts this hypothesis, and not all researchers agree that dietary protein increases catecholamines [78, 79, 80].

Drugs

A number of drugs, medical and otherwise, increase norepinephrine. This list is by no means comprehensive.

We recommend strongly against using these compounds to increase catecholamines; this section is here to provide information to people already taking these drugs on the advice of their doctors.

Antidepressants

Many antidepressants increase norepinephrine. These include tricyclic antidepressants (such as imipramine) and serotonin-norepinephrine reuptake inhibitors (SNRIs including venlafaxine) [81, 82, 83].

Nicotine

Nicotine increases norepinephrine release in animals and humans [84, 85, 86, 87].

However, this is an addictive drug which poses significant risks to people’s health and wellbeing. Furthermore, when people stop taking nicotine (either in cigarettes or by other means), their norepinephrine levels spike and then drop. In adolescents, this drop is associated with long-term risks of heart disease [87].

Because of its associated health risks, we recommend against using nicotine for any reason.

Bh5

Tetrahydrobiopterin, or Bh5, is a natural compound that is required for the human body to make neurotransmitters like norepinephrine. It is also available as a prescription medication for phenylketonuria. It increases the conversion of phenylalanine into tyrosine, which can then be converted into the catecholamines, including norepinephrine [88, 89, 90].

Tianeptine

Tianeptine is an antidepressant that activates opioid receptors, restores BDNF, and increases serotonin and norepinephrine in the spinal cord. Tianeptine may also increase norepinephrine in certain parts of the brain and decrease it in others [91, 92, 93, 94, 95].

COMT Inhibitors

As described above, COMT inhibitors reduce the breakdown of norepinephrine. Drugs in this category include Parkinson’s disease medications like entacapone and tolcapone [96, 97].

This article is the second of a three-part series:

• Part 1 (Norepinephrine 101)
• Part 3 (Too Much Norepinephrine)

Takeaway

Norepinephrine must stay in balance for the brain and body to stay healthy. Too little has been linked to low blood pressure, distractibility, and migraine. Norepinephrine is also lacking in some people with depression.

It is important for memory and cognitive function; low levels are associated with Alzheimer’s, Parkinson’s, and ADHD. People with chronic fatigue syndrome and fibromyalgia tend to poorly regulated norepinephrine systems. Low norepinephrine has also been tied to bipolar disorder and migraines.

Low norepinephrine can also be caused by genetic disorders, like DBH deficiency and CIPA, or by external factors like blood pressure drugs.

Some natural supplements and strategies may increase norepinephrine. If you suspect that you have low norepinephrine, however, the most important thing is to seek advice from your doctor.

Norepinephrine and the intestinal microbiome in the early stages of the demyelinating process: clinical and immunological parallels

The study of neuroimmune interactions is one of the most developing areas in the study of the pathogenesis of demyelinating diseases of the central nervous system (CNS) [1]. Numerous data indicate the importance of serotonin, dopamine, and norepinephrine as direct mediators of this interaction [2–5]. On the one hand, biogenic amines are involved in the development of neuropsychological disorders, and on the other hand, they modulate cell functions of both innate and adaptive immune responses [6, 7]. It has been shown that changes in the activity of neurotransmitter systems in multiple sclerosis (MS) can affect most of the known stages of the immunopathogenesis of the disease. The participation of biogenic amines in the regulation of the interaction between the brain-gut axis has also been established, which is especially important in the light of studying changes in the composition of the intestinal microbiota as an etiopathogenetic factor in MS [8, 9]. The prospects for using serotonergic, adrenergic, and dopaminergic drugs as pathogenetic therapy for MS are also discussed [10–13].

Sufficient data have been obtained indicating the diverse involvement of biogenic amines in the pathogenesis of RS. At the same time, the question of the role of biogenic amines in immunoregulation in the early stages of the demyelinating process remains poorly understood. In particular, how pronounced are the changes in the functioning of neurotransmitters in clinically (CIS) and radiologically isolated syndromes (RIS) and is it possible to modulate the subsequent course of MS or prevent the conversion of CIS and RIS into reliable MS by targeting biogenic amine receptors at an early stage of the disease? .

The paper presents a review of literature data on the role of biogenic amines, especially norepinephrine, in the regulation of psychoneuroimmune interactions in the early stages of the demyelinating process. Neuropsychological disorders, immunological aspects, changes in the composition of the intestinal microbiota in CIS, RIS and early MS, as well as the noradrenergic system in these conditions are discussed.

Neuropsychological disorders in CIS, RIS and early MS

Neuropsychological disorders are one of the most common symptoms of demyelinating diseases of the CNS, which may be due to the multifactorial etiology of the development of such conditions. In particular, depression and cognitive impairment in MS patients can develop as a reaction to a disabling condition that develops as a result of focal brain damage, inflammation in the CNS, and biochemical changes associated with dysfunction of neurotransmitters. Often, neuropsychological changes can be the first and only symptom of the demyelinating process in the CNS [13]. Moreover, psychoemotional stress is a frequent trigger factor for triggering a demyelinating disease, which allows it to be considered as one of the etiological causes of MS [1].

Identification of neuropsychological disorders may be important for more than just early diagnosis. An assessment of their severity may also have prognostic value. It has been shown that cognitive impairment can be an early marker of a progressive neurodegenerative process in MS, as well as a predictor of the conversion of CIS into MS [14–19].

Currently, the significance of other neuropsychological changes, in particular depressive and anxiety disorders, the prevalence of which in CIS can reach from 22 to 30% and from 36 to 100%, respectively, is being studied in detail [20-23]. It is important that a significant contribution to the genesis of anxiety disorder in this group of patients is made by the situation of uncertainty with the diagnosis and prognosis. With further monitoring of such patients, a decrease in the level of anxiety is noted, which is probably associated with adaptation to the condition and the implementation of coping strategies [20].

Similar data were obtained in the study of neuropsychological disorders in patients with early MS (the first 5 years after diagnosis) [24]. Thus, the prevalence of major depressive disorder in patients with early MS was 37%, anxiety disorder – 35%. The results of another study [25] showed that the more time passes from the onset of the disease, the lower the prevalence of anxiety disorder in patients with MS. The high level of anxiety in patients with early forms of MS, as in the case of CIS, is associated with adaptation to the fact of having a chronic disease [26].

Research is underway on the neuropsychological profile of patients with RIS and the possibility of identifying risk factors for conversion to MS. Cognitive deficit in RIS occurs in 20–30% of cases and is characterized by a decrease in the speed of information processing, impaired voluntary attention, episodic memory, and executive functions [27–30]. The incidence of cognitive impairment in RIS is comparable to that in CIS, however, for RIS, there are no convincing data indicating that cognitive impairment may be a risk factor for conversion to MS, as in CIS [17, 31].

In the course of the analysis of the neuropsychological characteristics of patients with RIS, it was found that in 50% of cases, patients have depression, which in 1/3 of cases meets the criteria for severe [32]. Patients with RIS are more likely to experience anxiety depression than those with CIS. A comparative analysis [32] showed that, in general, patients in the RIS group were more “prepared” for the appearance of mental symptoms compared to the CIS group and the control group. Also, somatization is more often detected in patients with RIS, and the quality of life, as a rule, is worse than in patients with CIS and the control group.

Thus, psychoemotional stress, considered as a risk factor for the development and exacerbations of MS [33, 34], may be of significant importance in RIS. According to studies [35, 36], in MS patients 4–9 weeks after severe negative stress, the risk of the appearance of new foci according to MRI increases. At the same time, a large number of T2 foci, as well as the appearance of new foci accumulating gadolinium, according to some authors [37], can be considered as a predictor of the conversion of RIS to MS, which suggests the effect of psychoemotional stress on the transformation of RIS to MS.

Changes in the composition of the intestinal microbiota in CIS, RIS and early MS

Current data indicate the involvement of the gut microbiota in the development of autoimmune diseases, including R.S. Potential possibilities for correcting the immune status are especially important in early forms of demyelinating diseases of the central nervous system in order to prevent the chronicization of the process and the transformation of diseases into RS. With the accumulation of data, recommendations are being formed to assess intestinal dysbiosis in identifying both CIS and RIS [38]. In this regard, it is relevant to assess the role of the microbiota in modulating the microbiota-immunity-CNS axis in CIS and RIS.

Changes in the microbiota at various levels have been shown in CIS and MS [39]. In particular, a decrease in antibodies to α1,3-galactose (Gal) in patients with CIS MS compared with healthy ones. Gal is produced by the microbiota, with anti-Gal antibodies appearing in the first months of life. Thus, in MS, a change in the content of Gal-producing bacteria is likely, which may indicate a decrease in microbiota diversity in CIS and MS.

S. Rolla et al. [40] found in patients with CIS a decrease in the content of Bacteroides spp. and overall microbiota diversity compared to healthy controls. According to the literature [41], stress on the host organism and, accordingly, an increase in the level of catecholamines, there is a decrease in the relative amount of Bacteroides spp. , as well as an increase in the relative amount of Clostridium spp. In addition, there is a higher frequency of detection of antibodies to Clostridium perfringens epsilon toxin in the blood serum of patients with CIS, MS, and optic neuritis compared with healthy controls [42]. It should be emphasized that literature data indicate a probable stimulating effect of adrenaline on C. perfringens. Thus, in the middle of the 20th century, it was shown that adrenaline at therapeutic concentrations leads to a 4-fold decrease in the number of C. perfringens [43].

Significant data are available on the effect of oral MS-modifying drugs (AMTs) on the growth of C. perfringens. According to the results of a study by L. Boyanova [44], drugs fingolimod, teriflunomide and dimethyl fumarate (as well as some chemically similar compounds) inhibit the growth of C. perfringens .

S. Rolla et al. [40] also noted that, in addition to a decrease in the content of Bacteroides spp. and the overall diversity of the intestinal microbiota, in the peripheral blood of patients with CIS, a fold increase in the percentage of Th27 cells expressing TLR2 and a decrease in T-regulatory cells (Treg) producing interleukin-10 (IL-10) are found, compared with the blood of healthy groups comparisons.

In addition to the immunoinflammatory component mediating the involvement of microbiota changes in the pathogenesis of CIS and RIS, there is the possibility of a direct effect of bacterial toxins on the pathogenesis of CIS, RIS and RS. According to some studies [44, 45], epsilon toxin C. perfringens has a certain tropism for the blood-brain barrier and CNS myelin, causing selective death of mature oligodendrocytes and demyelination.

Role of norepinephrine in neuroimmune interactions and regulation of the brain-gut axis

Norepinephrine as a mediator of neuroimmune interaction

The study of the properties of norepinephrine showed that, along with the regulation of autonomic and psycho-emotional functions, it is also able to participate in immunoregulation through the impact on cells of both innate and adaptive immune responses. It has been established that norepinephrine receptors are expressed by dendritic cells, T- and B-lymphocytes, etc. The immunomodulatory effect of norepinephrine can be mainly associated with the activation of β-2- and α-1-adrenergic receptors [46–51], despite their greater affinity with adrenaline. The involvement of norepinephrine in the pathogenesis of MS is confirmed by a reduced production of catecholamines by peripheral blood mononuclear cells (PBMCs) of MS patients, an increase in this production during interferon-β (IFN-β) therapy, as well as a positive effect of noradrenergic therapy on the course of experimental autoimmune encephalomyelitis (EAE) in animals. [52-54].

In MS, the anti-inflammatory effect of noradrenaline was also revealed, which may be associated with the suppression of a pathogenetically significant Th27 immune response. It was shown that the content of norepinephrine in the blood plasma of MS patients is reduced compared to healthy controls, while the production of pro-inflammatory cytokines interleukin-17 (IL-17) and interferon-γ (IFN-γ) by stimulated MNCPCs, as well as the percentage of Th27 -cells in peripheral blood, on the contrary, is increased. At the same time, the introduction of norepinephrine at a concentration of 10 ^–4 M in a culture of MNCPC of MS patients (both in the acute stage and in remission) and healthy people had an inhibitory effect on IL-17 and IFN-γ, although it was accompanied by some suppression of cell proliferation and a decrease in cell viability [55] . In addition, the effect of norepinephrine on the production of these cytokines by stimulated CD4 ⁺ T cells in patients with relapsing remitting MS and receiving glatiramer acetate therapy and healthy controls was studied [56]. The results were consistent with those obtained on the PBMC culture. Additionally, it was determined that norepinephrine retains its inhibitory effect on the production of IL-17 and IFN-γ at a lower concentration (10 ^-5 M), without affecting the proliferative ability of cells and their viability.

The modulating effect of norepinephrine was established in relation to other T-helper subpopulations pathogenetically significant in autoimmune diseases, in particular T-regulatory cells (Treg), which have an anti-inflammatory effect and maintain immunological tolerance. Thus, in the study by I. Pilipović et al. [51] showed that norepinephrine enhances Treg cell differentiation during EAE by increasing the production of transforming growth factor-β, one of the key factors in Treg cell differentiation.

In addition, the anti-inflammatory effect of norepinephrine on dendritic cells was described [46] — norepinephrine suppressed lipopolysaccharide-stimulated production of pro-inflammatory cytokines IL-6, IL-12p70, and IL-23 by dendritic cells. Such dendritic cells had a greater ability to induce the development of FoxP3 ⁺ -Treg cells. At the same time, according to other authors [48], norepinephrine is able to enhance the Th27 immune response induced by dendritic cells (stimulated by muramyl dipeptide). It must be taken into account that the effect of norepinephrine on the same cell populations may differ depending on the stimuli used, as well as the working concentrations of norepinephrine.

In general, research data indicate the presence of various mechanisms that mediate the immunomodulatory effect of norepinephrine. Importantly, in the context of demyelinating diseases, the effect of norepinephrine on immune system functions has been studied mainly in EAE models or in MS in vitro cell culture models .

Effect of norepinephrine on the functioning of the intestinal microbiota

Recent studies have shown that various representatives of the intestinal microbiota are capable of producing biogenic amines, including norepinephrine. Many bacteria have both their own set of enzymes for the synthesis of monoamines and are capable of capturing them from the environment (for example, Lactobacillus salivarius biofilms ) [57–59].

The intestine is characterized by a relatively high content of norepinephrine, and its level increases in the presence of bacterial flora. In addition to their own synthesis, bacteria also have a receptor apparatus for the perception of norepinephrine stimulation (bacterial QseC sensory kinase is the most probable analog of adrenoreceptors) [57, 60].

Numerous studies have identified the stimulating effect of norepinephrine on the microbiota. In addition to stimulating bacterial growth, norepinephrine can increase the expression of genes responsible for virulence [61, 62]. In particular, norepinephrine increases the expression of Shiga toxin produced by the pathogenic enterohemorrhagic strain Escherichia coli O157:H7 and increases the adhesion and invasion of E. coli and Salmonella spp. to the intestinal wall of mammals [63, 64]. It is the presence of catecholamines in the intestine that can explain the phenomenon of the sufficiency of small amounts of bacteria such as E . coli O157: H7, for a significant pathological effect [65, 66].

Norepinephrine directly affects the microbiota-immunity axis. It has been shown that norepinephrine enhances the penetration of the pathogenic strain of Escherichia coli E . coli O157: H7 and Salmonella choleraesuis in Peyer’s patches (intestinal lymphoid tissue). At the same time, no such effect was observed with respect to nonpathogenic E. coli [66]. Many strains are characterized by sensitivity to norepinephrine, rather than to adrenaline, which in some cases even acts as a competitive antagonist with respect to norepinephrine and dopamine [64].

The stimulatory effect of noradrenaline on the intestinal microbiota is explained by various mechanisms. In addition to the receptor mechanism, this may also be the catecholamine-mediated release of iron from lactoferrin and transferrin (iron carrier proteins), which makes it available for bacterial uptake [66]. The contribution of the norepinephrine receptor pathway to the microbiota was assessed by knockout of β-1 and β-2 adrenoreceptors in mice. This led to an increase in the prevalence of Bacilli lactobacillales in the intestine, which was associated with an increase in the production of anti-inflammatory short-chain fatty acids (butyrate, propionate and acetate) [67, 68] and a decrease in the number of circulating CD4 ⁺ IL-17 ⁺ T cells [68].

A significant contribution to the norepinephrine-microbiota relationship is made by α-adrenoreceptor signaling, since α-adrenoceptor (but not β-adrenoceptor) antagonists are able to block the ability of norepinephrine to cause the growth of a number of intestinal, in particular pathogenic gram-negative, bacteria [66, 69].

The task of modern medicine is to identify the pathological process characteristic of MS as early as possible and start a highly specific immunomodulatory treatment that prevents the development of irreversible immunological and neurodegenerative changes. According to prospective studies [70, 71], clinically significant MS develops in 60–70% of patients within 20 years of the discovery of CIS. A high probability of developing MS is also noted in patients with RIS (up to 30% in the first 5 years after the onset of the disease) [72]. Determination of the molecular biological characteristics of CIS and RIS, which combine these changes with MS, is an urgent scientific problem, the solution of which will allow timely initiation of therapy at the earliest stages of the demyelinating process, including at the subclinical stage, thus preventing the development of a highly incapacitating CNS disease.

The results of studies [10-12, 73] indicate the importance of neurotransmitters in the pathogenesis of demyelinating diseases of the CNS. With the accumulation of data, there are grounds for discussing the prospects for the use of serotonergic, dopaminergic and noradrenergic therapy as an additional pathogenetic treatment of MS (for example, in addition to basic MS therapy with IFN-β or glatiramer acetate). With the advent of data indicating the critical role of the intestinal microbiota in the pathogenesis of autoimmune diseases, as well as the effect of serotonin, dopamine and norepinephrine on the intestinal microbiota, interest in the study of biogenic amines as central regulators of the brain-gut-immune system interaction has increased significantly.

Taking into account changes in the composition of the intestinal microbiota, as well as the presence of neuropsychological disorders, it can be assumed that biogenic amines have an important pathogenetic significance in CIS and RIS. At the same time, the state of the adrenergic and noradrenergic systems in early forms of the demyelinating process is currently insufficiently studied. The work carried out on the study of noradrenaline in CIS and early MS is mainly associated with the study of autonomic dysfunction in these patients. It has been shown that the presence of symptoms of autonomic dysfunction is accompanied by a decrease in the concentration of norepinephrine in blood plasma [74], and a low concentration of epinephrine in blood plasma is a predictor of a new exacerbation in patients with CIS [75]. Current studies have not yet assessed immunological parameters or gut microbiota composition, making it difficult to understand the role of norepinephrine in terms of immunomodulatory effects.

The study of the “brain-gut-immune system” axis in early forms of the demyelinating process is just beginning to develop. The current data are insufficient to determine a therapeutic target, targeting which would reduce the risk of conversion of CIS and RIS to RS. Perhaps further study of this issue will allow us to assess the likelihood of preventing the chronization of the demyelinating process by acting on biogenic amine receptors.

The submitted work has not been previously published in other publications.

The work was carried out within the scope of the GA AAAA-A19-11

-0.

The authors declare no conflict of interest.

The authors declare no conflicts of interest.

Credits

Sviridova A.A. — https://orcid.org/0000-0003-1086-9052

Kabaeva A.R. — https://orcid.org/0000-0002-0982-8520

Rogovsky V.S. — https://orcid.org/0000-0002-3682-6571

Kozhieva M.Kh. — https://orcid.org/0000-0001-6665-8655

Melnikov M.V. — https://orcid.org/0000-0001-6880-3668

Boyko A.N. — https://orcid.org/0000-0002-2975-4151

How to quote:

Sviridova A. A., Kabaeva A.R., Rogovsky V.S., Kozhieva M.Kh., Melnikov M.V., Boyko A.N. Norepinephrine and the gut microbiome in the early stages of the demyelinating process: clinical and immunological parallels. Journal of Neurology and Psychiatry. S.S. Korsakov. 2019;119(10, issue 2):28-34. https://doi.org/10.17116/jnevro201911910228

Corresponding author: Mikhail Valerievich Melnikov — e-mail: [email protected]

in the intestinal microbiota, which makes it difficult to understand the role of norepinephrine in terms of immunomodulatory effects.

The study of the brain-gut-immune system axis in early forms of the demyelinating process is just beginning to develop. The current data are insufficient to determine a therapeutic target, targeting which would reduce the risk of conversion of CIS and RIS to RS. Perhaps further study of this issue will allow us to assess the likelihood of preventing the chronization of the demyelinating process by acting on biogenic amine receptors.

Sviridova A.A., Kabaeva A.R., Rogovsky V.S., Kozhieva M.Kh., Melnikov M.V., Boyko A.N. Norepinephrine and the gut microbiome in the early stages of the demyelinating process: clinical and immunological parallels. Journal of Neurology and Psychiatry. S.S. Korsakov. 2019;119(10, issue 2):28-34. https://doi.org/10.17116/jnevro201911910228

Corresponding author: Mikhail V. Melnikov — e-mail: [email protected]

Neurotransmitters and their role in neural communication

Neurotransmitters and their role in neural communication

09/02/2021
Number of views 87395

Neurotransmitters or neurotransmitters are chemical molecules released by neurons. They ensure the transmission of messages from one neuron to another in synapses.

English name:

neurotransmitters

Synonyms:

neurotransmitters, neuromodulators

See also:

Alzheimer’s disease
Parkinson’s disease

Contents

1. How neurotransmitters work
2. Types of neurotransmitters and their functions
3. Neurotransmitters and diseases

Neurotransmitters have been found in 1921 years old by biologist Otto Loewy, who later received the Nobel Prize for his work. Prior to this, it was believed that interneuronal communication (between neurons) is the result of electrical communication. Lowy found this concept wrong, showing that neurons communicate with each other through the release of chemicals called neurotransmitters. From 1921 to the present day, more than 60 different types of neurotransmitters have been discovered.

Neurotransmitters play an important role in neural communication. They are chemical messengers that carry messages between nerve cells (neurons) and other cells in your body, affecting everything from mood to involuntary movements. This process is commonly referred to as neurotransmission or synaptic transmission.

The good functioning of neurotransmitters provides us with a stable functioning of the nervous system.

How neurotransmitters work

To send messages throughout the body, neurons must send signals to communicate with each other. But there is no physical connection between them, only the point of contact between two nerve cells, which is called a synapse.

To communicate with the next cell, a neuron sends a signal across the synapse by diffusion of a neurotransmitter.

Neurotransmitters affect neurons in three ways: they can be excitatory, inhibitory, or modulatory. The excitation emitter generates a signal in the receptor neuron, called an action potential. The braking transmitter prevents this. Neuromodulators regulate groups of neurons.

Some neurotransmitters, such as dopamine, have both excitatory and inhibitory effects depending on the receptor.

Types of neurotransmitters and their functions

Here are the most important neurotransmitters and the roles they play:

• Acetylcholine. The main functions of acetylcholine and its mechanisms of action: among the various types of neurotransmitters, acetylcholine is the neurotransmitter responsible for muscle stimulation. It is responsible for the activation of motor neurons and is also involved in various areas of the brain associated with learning, memory, or arousal. In addition, acetylcholine is considered an ally in the fight against neurological disorders.

  The main function of acetylcholine is to improve cognitive skills. It is the basis of memory function, concentration ability and logical reasoning. It is also responsible for the transition from the state of alertness to the state of sleep.

  Acetylcholine is localized in various parts of the central nervous system, as well as in the synapses of the glands and muscles.

• Dopamine. It is associated with pleasure and feelings of relaxation.

Among the main functions of dopamine is the regulation of memory, learning, and it plays an important role in decision making. Motivation and curiosity are also associated with this neurotransmitter.

Dopamine is responsible for regulating the emotions of pleasure. If we use nicotine or alcohol regularly, they increase the levels of dopamine in our body, causing this feeling of pleasure and relaxation.

This neurotransmitter is found in the autonomic nervous system.

• Norepinephrine. Also known as the stress hormone due to its dual role as a hormone and as a neurotransmitter. It is a type of neurotransmitter that has an excitatory function responsible for activating the sympathetic nervous system. It is involved in fight-or-flight behavior in response to stress.

  Norepinephrine is associated with heart rate and is involved in brain attention and problem solving processes. Among its functions is also the regulation of the state of physical and mental arousal.

  This type of neurotransmitter is localized mainly in the central nervous system, as well as in certain areas of the sympathetic region of the autonomic nervous system.

• Gamma-aminobutyric acid (GABA). This neurotransmitter has an inhibitory function on the nervous system, preventing overexcitation to avoid reactions such as anxiety or fear. Alcohol and drugs can affect this neurotransmitter, creating a sense of subjective control. It is the most abundant excitatory neurotransmitter (75%) in the central nervous system.

  GABA plays an important role in the control of motor activity and vision, behavior and response to stress. In addition, it is an important ally in the fight against anxiety. It is found in the brain and cerebral cortex.

• Serotonin. It is also known as the hormone of happiness. That is, it performs two functions in our body: as a hormone and as a neurotransmitter.

  Serotonin plays an important role in the process of digestion, in the regulation of body heat, and also has a great influence on sexual desire. This neurotransmitter is present in various areas of the central nervous system.

• Glutamate. It is associated with the neurotransmitter GABA and is most abundant in the central nervous system. Paradoxically, excess glutamate has a toxic effect on our body, leading to the death of neurons.

  This type of neurotransmitter is associated with memory and learning functions, as well as more complex cognitive functions. Thus, an imbalance of this neurotransmitter can cause neurodegenerative pathologies.

  Glutamate is found in various areas of the central nervous system.

Neurotransmitters and diseases

Billions of neurotransmitter molecules are constantly at work to keep the brain working and control everything from breathing to heartbeat to the ability to concentrate.

Many neurotransmitters are associated with a number of diseases:

• Alzheimer’s disease and Parkinson’s disease are associated with acetylcholine deficiency. In patients suffering from Alzheimer’s disease, up to 90% loss of acetylcholine is observed in the brain.

• Dopamine is associated with Attention Deficit Hyperactivity Disorder (ADHD) as a deficiency of this neurotransmitter causes problems with concentration. Dopamine is also associated with bipolar disorders in their manic and hypomanic phases. Schizophrenia and Parkinson’s disease are also associated with this neurotransmitter. In the case of schizophrenia, due to an excess, and in the case of Parkinson’s disease, due to a lack of dopamine in the motor areas, causing an uncontrolled tremor.

• Norepinephrine deficiency is associated with depressive disorders . Stress tends to deplete our reserves, while some drugs, such as amphetamines or drugs, increase our levels dramatically. Low levels of norepinephrine reduce sexual appetite.

• When GABA levels are low, our body can suffer from anxiety disorders and its complete absence is associated with epileptic episodes. Low GABA levels can cause mania and panic attacks.

• Serotonin deficiency in our body is associated with diseases such as depression, obsessive-compulsive disorder (OCD), as well as aggression, drug addiction, eating disorders and insomnia .

• Too low glutamate levels are associated with motor neuron diseases . The main comorbidity is excitotoxicity, a process in which neurons are severely damaged or destroyed due to excessive activity. Excitotoxicity is associated with apathy, and it is associated with neurodegenerative diseases such as Huntington’s disease, Alzheimer’s disease and Parkinson’s disease. The high level of glutamate in our body is bound with epileptic episodes ..

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