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Neurotransmitters: minute chemicals delivering powerful messages

The nervous system of human beings is undoubtedly one of the most complex and challenging systems to try and understand. Whilst we all have a good understanding of brain health, and what to do to keep our brain healthy (such as learning languages or musical instruments, engaging in hobbies, meditation and social interaction), you may not know much about the smaller, minute chemical details of what makes our nervous system tick. These chemicals are known as neurotransmitters, and their functions are far more expansive and important to your health than you may realize.

Every day, your nervous system receives millions of signals from sensory organs such as the eyes, ears, skin, nose and tongue. These actions allowing us to read, listen to music or taste food are relatively straightforward to comprehend. However, your nervous system also controls the movement of every muscle fiber in your body (including the cardiac muscle of the heart, and the smooth muscle of your entire digestive tract). The nervous system also responds to the ever-changing chemical environment of your body,such as fluctuations in acidity/alkalinity, inflammatory changes and mood, to name just a few. It is bewildering to contemplate just how the nervous system achieves all this. By looking at individual neurotransmitters, we can begin to appreciate the minute yet utterly powerful actions of these chemical messengers.

Acetylcholine
Acetylcholine (ACh) was the first neurotransmitter ever discovered. Out of all neurotransmitters, ACh is probably the most far reaching in terms of effect. It is involved in nerve impulse transmissions in both sympathetic (stress) and parasympathetic (rest/digest) responses throughout every cell and organ in the body.

Its name simply comes from its chemical structure; ‘acetyl’ is a very small chemical species that contains only a little carbon and hydrogen (C3H6), while choline is more like a lipid (fat). We make our own ACh; we do not need to obtain it from food or supplements. Without ACh, our nervous system would simply cease to function. Diseases like Alzheimer’s disease show marked
reduction in ACh concentrations in specific areas of the brain, while Myasthenia gravis is an autoimmune disease affecting the role of ACh in muscle contraction.

Histamine
Generally not appreciated as a neutransmitter, histamine is well known for its role in allergy and inflammation. However, its role as a neurotransmitter is essential for preventing sleep, keeping us awake (hence the reason why antihistamines generally make us drowsy). It is synthesized in the body via the amino acid, histidine. Again, histidine is readily supplied by most foods in our diet. Many people on the path to healing allergies and food intolerances are eating a low histamine diet to reduce the occurrence of hives, rashes, sneezing and gut pain. However, the strong link between histamine, the brain and nervous system mean that migraines, drowsiness and moodiness are reported as alleviated for many people adopting low histamine diets.
Dopamine
Dopamine is synthesized via several steps that begin with an essential component of our diet, the amino acid phenylalanine. Phenylalanine is firstly converted to tyrosine (in the liver). After several steps, tyrosine is then converted to Dopamine. Interestingly, this process relies heavily on vitamin B6, and would not occur if we did not consume any phenylalanine in the diet. Luckily, phenylalanine is found in most foods, regardless of the diet we follow.

Dopamine is rather versatile. It has a role to play in movement, memory, mood, pleasure/reward, behavior, sleep, learning and attention. Both excessive and insufficient levels of dopamine are implicated in ill health, spanning both physical and mental health conditions.

Conditions associated with abnormalities of dopamine function include Parkinson’s disease (dopamine deficiency) and possibly Schizophrenia (overstimulation of specific dopamine receptors in the brain). Low dopamine activity has also been linked to addiction, ADHD, risk-taking and strong reward/pleasure-seeking behaviors.

Adrenaline and noradrenaline
Adrenaline (epinephrine) is both a neurotransmitter and a hormone. It is synthesized in the adrenal glands and some neurons. It is actually synthesized from dopamine; hence it follows the same pathway as dopamine production, with a few extra chemical reactions to finally produce adrenaline. It is an excitatory neurotransmitter, with low levels being associated with fatigue, inability to focus, poor attention span, difficulty sleeping and difficulty losing weight. Interestingly, these are often symptoms described by individuals under high stress, with adrenal exhaustion.

Noradrenaline (norepinephrine) is related to adrenaline, but is farmore widespread throughout the body. Like adrenaline, it is excitatory; thus it increases wakefulness, alertness and vigilance. It is paramount during stress, the ‘fight or flight’ response allowing us to focus and retrieve memories. It also increases restlessness and can promote anxiety. Generally, high levels are associated with prolonged stress and ADHD.

Serotonin
Serotonin is regularly referred to by its more chemical name, 5-hydroxytryptamine (5-HT). Serotonin is another of our neurotransmitters derived from an amino acid; in this case, tryptophan. Tryptophan is an essential amino acid; we must supply it to our body via our diet.

90% of serotonin in the human body is located in the gastrointestinal (GI) tract, making this neurotransmitter extremely interesting to medical science. Not only does serotonin regulate motility of the GI tract, it is involved in central nervous system functions such as sleep, appetite, mood, learning and memory. Clinically, abnormalities of serotonin function have been linked with an array of health conditions from over-eating and obesity, through to major depression, obsessive-compulsive disorder (OCD) and anxiety. The emerging scientific evidence linking gut health with mental health is due in part to the activity of serotonin in these two anatomically separate, yet biochemically linked organs.

Glycine
Glycine is an amino acid neurotransmitter, which is non-essential in the diet. It can be synthesized in the human liver, but this relies on the adequate supply of activated vitamin B9 from our diet. Glycine is simple in its molecular structure (it is the smallest amino acid). It functions primarily in the spinal cord, having inhibitory
effects on information that co-ordinates movement, vision and hearing. It assists in reducing hyper excitability of the nervous system, with some studies linking low glycine levels with hyperactivity, schizophrenia, bipolar disorder and epilepsy.

Glutamate
Glutamate is the major excitatory neurotransmitter of our nervous system. It links in with pathways for many of the other neurotransmitters, and receptors responding to glutamate are located throughout our brain and spinal cord. Glutamate comes from the amino acid, glutamic acid (it is the base pair of this acid). Humans synthesize glutamate within our nerve cells from a range of precursor substances, including glutamine. As glutamate is excitatory in its role, it’s responsible for cognition, memory and learning. In diseases involving glutamate, this neurotransmitter can accumulate outside of nerve cells, continually stimulating them and leading to excitotoxicity. This can eventually lead to destruction of functional nerve tissue. Examples include Alzheimer’s disease and the cascade of destruction that follows a stroke.

Gamma-amino butyric acid (GABA)
GABA is the inhibitory neurotransmitter partner of the excitatory glutamate. These two neurotransmitters work together to balance brain activity. While it may sound negative to have inhibitory effects on the nervous system, GABA is vital for the sedation that precedes sleep, and it is imperative for relaxation. Humans synthesize GABA in the brain from its excitatory partner, glutamate. Again, vitamin B6 is required for this biochemical conversion. Supplements of GABA do exist, mainly for the treatment of hyperactivity and poor sleep. However, there is no evidence GABA taken orally will cross the blood brain barrier to reach GABA target nerve cells in the brain. Additionally, the human body is very proficient at GABA regulation, meaning supplementation is likely ineffective.

Takeaway points

Inhibitory (Calming) NeurotransmittersGABA
Serotonin
Glycine
Acetylcholine (both)
Dopamine (both)
Excitatory (Stimulating)NeurotransmittersDopamine (both)
Adrenaline
Noradrenaline
Glutamate
Histamine
Acetylcholine (both)

Written by Annalies Corse, ND.

References:
1 Waymire, J. Acetylcholine Neurotransmission. Neuroscience Online. Department of Neurobiology and Anatomy, The UT Medical School at Houston. Available at: http://neuroscience.uth.tmc.edu/s1/chapter11.html
2 Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System: Workshop Summary. Available at: http://www.ncbi.nlm.nih.gov/books/NBK62187/
3 Lopez-Corcuera, B. (2001). Glycine neurotransmitter transporters: an update. Molecular Membrane Biology. 18(1): 13-20. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11396606
4 University of Bristol. Serotonin. A molecule of happiness. Available at: http://www.chm.bris.ac.uk/motm/serotonin/home1.htm
5 Maintz, L., Novak, N. (2007). Histamine and Histamine Intolerance. The American Journal of Clinical Nutrition. Available at: http://ajcn.nutrition.org/content/85/5/1185.longGoldstein, D. (2010). Adrenaline and Noradrenaline. Citable Reviews in the Life Sciences. Available at: http://www.els.net/WileyCDA/ElsArticle/refId-a0001401.html

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