Serotonin
Serotonin or 5-Hydroxytryptamine or 5HT is a monoamine neurotransmitter derived from tryptophan. It can be found in the central nervous system, gastrointestinal tract, and platelets.
Synthesis[edit | edit source]
Serotonin can function as both a peripheral hormone and a neurotransmitter.
Peripheral hormone[edit | edit source]
Around 95% of the body's serotonin is produced in the gut. More specifically, cells in your intestines called enterochromaffin cells produce serotonin and release it into the bloodstream. Platelets store this serotonin and release it when needed. Typically the level of serotonin in your blood is around 1-5 ng/mL. When your inflammatory systems activate, your peripheral serotonin levels can increase 1000-fold.[1]
Neurotransmitter[edit | edit source]
Since serotonin is water soluble, it can't cross the blood-brain barrier (BBB) easily. So the central nervous system produces its own supply of serotonin separate from the rest of the body. This supply of serotonin is synthesized in the raphe nuclei of the brainstem.[1]
L-Tryptophan → L-5-Hydroxytryptophan (5HTP) → 5-hydroxytryptamine (serotonin, 5HT)[2]
Function[edit | edit source]
Serotonin is a neurotransmitter and is activated by threats to homeostasis. According to Pereira et al. 2021), serotonin is linked to the regulation of:
- dysautonomia
- dyspnea
- fatigue
- glucose control
- hypothyroidism
- immune system functioning
- proprioception, and
- sensory sensitivity[3]
Serotonin acting drugs[edit | edit source]
Selective serotonin reuptake inhibitors (SSRIs), the most popular class of antidepressants, and selective serotonin and norepinephrine reuptake inhibitors (SNRIs) have proved ineffective in ME/CFS.[4][5] SSRIs indiscriminately modulate serotonin.[3]
In human disease[edit | edit source]
ME/CFS[edit | edit source]
The CRFR2 upregulation hypothesis of ME/CFS, which is the theory behind the clinicial trials of CT38, proposes that serotonin is dysregulated in ME/CFS, and that excessive serotonin desensitizes 5HT1A, which then leaves serotonin elevated and a loss of homeostasis.[3]
Notable studies[edit | edit source]
- 2015, A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice
- 2008, Genetic evaluation of the serotonergic system in chronic fatigue syndrome
- 2004 Reduction of serotonin transporters of patients with chronic fatigue syndrome
- 1997, Blunted serotonin-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome.
Learn more[edit | edit source]
See also[edit | edit source]
References[edit | edit source]
- ↑ 1.0 1.1 Kanova, Marcela; Kohout, P (May 3 2021). "Serotonin—Its Synthesis and Roles in the Healthy and the Critically Ill". International Journal of Molecular Sciences. 22 (9). doi:10.3390/ijms22094837. Check date values in:
|date=(help) - ↑ Hoglund, Erik; Overli, Oyvind; Winberg, Svante (April 8, 2019). "Tryptophan Metabolic Pathways and Brain Serotonergic Activity: A Comparative Review". Frontiers in Endocrinology. 8 (10). doi:10.3389/fendo.2019.00158.
- ↑ 3.0 3.1 3.2 Pereira, Gerard; Gillies, Hunter; Chanda, Sanjay; Corbett, Michael; Vernon, Suzanne D.; Milani, Tina; Bateman, Lucinda (2021). "Acute Corticotropin-Releasing Factor Receptor Type 2 Agonism Results in Sustained Symptom Improvement in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Frontiers in Systems Neuroscience. 15: 84. doi:10.3389/fnsys.2021.698240. ISSN 1662-5137. PMC 8441022. PMID 34539356.
- ↑ Carruthers, BM; van de Sande, MI; De Meirleir, KL; Klimas, NG; Broderick, G; Mitchell, T; Staines, D; Powles, ACP; Speight, N; Vallings, R; Bateman, L; Bell, DS; Carlo-Stella, N; Chia, J; Darragh, A; Gerken, A; Jo, D; Lewis, DP; Light, AR; Light, KC; Marshall-Gradisnik, S; McLaren-Howard, J; Mena, I; Miwa, K; Murovska, M; Stevens, SR (2012), Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners (PDF), ISBN 978-0-9739335-3-6
- ↑ Carruthers, Bruce M.; Jain, Anil Kumar; De Meirleir, Kenny L.; Peterson, Daniel L.; Klimas, Nancy G.; Lerner, A. Martin; Bested, Alison C.; Flor-Henry, Pierre; Joshi, Pradip; Powles, AC Peter; Sherkey, Jeffrey A.; van de Sande, Marjorie I. (2003), "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols" (PDF), Journal of Chronic Fatigue Syndrome, 11 (2): 7–115, doi:10.1300/J092v11n01_02
