What is Serotonin
Serotonin (also called 5-HT because of its chemical name, 5-hydroxytryptamine) is a neurotransmitter that is produced naturally in our body. As a neurotransmitter, serotonin carries signals along and between nerve cells (neurons). It’s found mainly in the intestines but also in the central nervous system (CNS) and the blood platelets.
Biosynthesis of Serotonin
Serotonin is synthesised in serotonergic terminals from the amino acid tryptophan, which competes with tyrosine and the branched chain amino acids for transport across the blood-brain barrier. Tryptophan is converted to 5-Hydroxytryptophan (5-HTP) through the process of hydroxylation facilitated by the enzyme tryptophan hydroxylase (Tph-1). 5-HTP is the intermediate metabolite of the essential amino acid tryptophan in the biosynthesis of serotonin and with the help of the enzyme aromatic amino acid decarboxylase (AAAD) undergoes decarboxylation in which is converted into serotonin, or in other words 5-hydroxytryptamine (5-HTP).
Figure 1. Biosynthesis of Serotonin from Tryptophan
The Role of Serotonin in the Body
Serotonin has an important role in a number of bodily functions. It is vital for positive mood, good appetite and sleep, digestion, sexual function, blood clotting and bone density. As we get older serotonin levels start declining. Food cravings for simple carbs and salty foods often stem from low serotonin levels. These foods may offer a quick fix, but it is one that does not last. Thus a vicious cycle of more food cravings occur which could potentially become risk factor for the development of many illnesses.
Positive mood and restful sleep
When serotonin levels are optimal we experience a great mood during the day and a restful sleep at night. When serotonin levels are low so is our self-confidence. This is because serotonin keeps the right and left hemisphere of the brain in balance. When this balance is compromised it would result with disconnection between the brain's left side's rationality and right side's creativity and as a consequence lead to low mood, depression and trouble falling asleep.
Serotonin also plays an important role in the production of melatonin (the sleep hormone). Within the pineal gland, serotonin is acetylated and then methylated to produce melatonin which is an important regulator for normal sleep patterns.
Figure 2. Biosynthesis of Melatonin from Serotonin
In the brain, serotonin acts as a neurotransmitter or chemical message which is being sent across the gap called the synapse between nerve cells. The cell sending the message, called the pre-synaptic cell, releases serotonin into the synapse. The serotonin is taken in by the receiving, post-synaptic cell, or be taken back by the pre-synaptic cell. In depression the post-synaptic cell doesn't take in enough serotonin and the message gets lost. The most commonly used drugs against depression are serotonin selective re-uptake inhibitors (SSRIs) which decrease the ability of the pre-synaptic cell to reuptake the serotonin, leaving the message in the synapse longer and giving the post-synaptic cell a better chance of receiving the serotonin.
The predominant site of serotonin synthesis, storage, and release is the enterochromaffin (EC) cells of the intestinal mucosa. Within the intestinal mucosa, serotonin released from EC cells activates neural reflexes associated with intestinal secretion, motility and sensation. On this way it stimulates the production and release of gastric and colonic mucus important for normal digestion. Dysregulation of serotonin would lead to diarrhoea or constipation. Moreover, conditions such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) have been associated with low serotonin levels (Costedio et al., 2007). This is because serotonin can act as a pro-inflammatory molecule and can modulate immune cell function in the gut.
Serotonin is also involved in food intake control, with serotonin high levels reducing total energy intake or selectively reducing carbohydrate selection over protein. Serotonin exhibits control over hunger through several receptors with different functions. There are seven different families of 5-HT receptors, and in some of these families there are many receptor subtypes, mainly 5-HT1 and 5-HT2 receptors. These receptors are responsible for the reduced food intake associated with serotonin. Recent studies have also demonstrated an ability of serotonin to activate neurons and receptors such as melanocortin-4 receptors ( MC4Rs) which curb appetite, and at the same time block other neurons that normally act to increase appetite (Sharma & Sharma, 2012).
Serotonin contributes to the formation of blood clots. It is released by platelets (disc shaped red blood cells) when there is a wound. The resulting vasoconstriction, or narrowing of the blood vessels, reduces blood flow and helps blood clots to form. When activated, the platelets release the contents of small packages that they carry called delta granules. These packages contain calcium, various energy-containing molecules, and serotonin. When the delta granules are released by activated platelets, the serotonin and other molecules work in the injured area to amplify the coagulation response.
The serotonin derived from the GI tract and transported through the circulation is the major source for skeletal serotonin. Bone cells possess functional pathways for both responding to and regulating the uptake of serotonin. Serotonergic receptors have been identified in all the major bone cell types (osteoblasts, osteocytes, and osteoclasts) and stimulation of these receptors influence bone cell activities (Gustafsson et al., 2006).
How to Boost Serotonin Levels
- Low serotonin levels could mean that the brain is making less serotonin, or has fewer receptors for it, or those receptors just aren't grabbing on to the serotonin very well. It can also mean the serotonin that's made is broken down too soon, or that the serotonin that's released out into the synapse is sucked too quickly back into the pre-synaptic neuron. Changing any one of these factors can increase serotonin activity (Birdsall, 1998).
- One way to increase serotonin levels is by frequent exposure on sunlight. This is because serotonin production in the brain is directly related to the duration of bright sunlight. Recent research provides more evidence that lack of sunlight and reduced serotonin levels are important in the development of seasonal affective disorder (SAD). People with SAD develop symptoms of depression in the winter months when there is less daylight. Symptoms include difficulty concentrating, low energy or fatigue, loss of interest in daily activities, moodiness, and sleeping excessive amounts.
- The positive effect sunlight has on serotonin levels is because it enables synthesis of Vitamin D. Serotonin synthesis, release, and function in the brain are modulated by vitamin D and the 2 omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Brain serotonin is synthesized from tryptophan by tryptophan hydroxylase 2, which is transcriptionally activated by Vitamin D hormone. Therefore, inadequate levels of Vitamin D and Omega-3 fatty acids would lead to reduced production of serotonin (Patrick & Ames, 2015).
- Exercise is equally important to boost serotonin levels. In particular, aerobic exercise, like running and biking, is most likely to boost serotonin. However, yoga works too. Two different mechanisms may be involved in this effect. As reviewed by Jacobs & Fornal (1999), motor activity increases the firing rates of serotonin neurons, and this result in increased release of serotonin. In addition, exercise would also increase the levels of the serotonin precursor, tryptophan which is important for the synthesis of serotonin.
- Meditation practices have various health benefits including the possibility of increasing serotonin levels, preserving cognition and preventing dementia. While the mechanisms remain investigational, studies show that meditation may affect multiple pathways that could play a role in brain aging and mental health. Researches have shown that activities like mindfulness have a direct impact on the brain’s production of serotonin levels. It is thought that meditation "bathes" neurons with an array of feel-good chemicals. Meditation also reduces stress-induced cortisol secretion and this could have neuroprotective effects potentially via elevating levels of brain derived neurotrophic factor (BDNF). Meditation may also potentially have beneficial effects on lipid profiles and lower oxidative stress, both of which could in turn reduce the risk for cerebrovascular disease and age-related neurodegeneration. Further, meditation may potentially strengthen neuronal circuits and enhance cognitive reserve capacity (Xiong & Doraiswamy, 2009).
- Birdsall, T.C (1998). 5-Hydroxytryptophan: a clinically-effective serotonin precursor. A Journal of Clinical Therapeutic. 3 (4), 271-280.
- Costedio, M.M., Hyman, N., Mawe, G.M et al. (2007). Serotonin and its role in colonic function and in gastrointestinal disorders. Diseases of the colon and rectum. 50 (3), 376-388.
- Gustafsson, B.I., Thommesen, L., Stunes, A.K. et al. (2006). Serotonin and fluoxetine modulate bone cell function in vitro. Journal of Cell Biochemistry. 98 (6), 139–151.
- Jacobs, B.L., Fornal, C.A. (1999). Activity of serotonergic neurons in behaving animals. Neuropsychopharmacology . (9) 21, 9-15.
- Patrick, R.P., Ames, B.N. (2015). Vitamin D and the omega-3 fatty acids control serotonin synthesis and action. The Faseb Journal. 29 (6), 14-23.
- Sharma, S., Sharma, J. et al. (2012). Regulation of Appetite: Role of Serotonin and Hypothalamus. Iranian journal of pharmacology & therapeutics. 12 (2), 73-79.
- Xiong, G.L., Doraiswamy, P.M. (2009). Does Meditation Enhance Cognition and Brain Plasticity? The New York Academy of Sciences. 28 (9), 33-46.
- Images: Morning exercise photo created by marymarkevich - www.freepik.com
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