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Sunday, 15 December 2013

The Effects of Hormone Serotonin (4)

Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter derived from tryptophan,  primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS). In Gut, serotonin regulates intestinal movements, in CNS, it regulates mood, appetite, sleep, memory and learning, etc.
31. Monoamine and diseases
The monoamine hypothesis has been recognized for over half a century as a reference point to understanding electrical dysfunction associated with disease states, and/or regulatory dysfunction related to synaptic, centrally acting monoamine concentrations (serotonin, dopamine, norepinephrine, and epinephrine). According to the study by the Clinical Research, Neuro Research Clinics, centrally acting monoamine concentrations are indistinguishable in subjects with and without disease symptoms and/or regulatory dysfunction. Analysis of centrally acting monoamine concentrations in the endogenous state reveals a significant difference in day-to-day assays performed on the same subject with and without monoamine-related disease symptoms and/or regulatory dysfunction(31).

32. Metabolic syndrome: a brain disease
According to the study by The TsimTsoum Institute, Krakow, Silesia, Poland, increased sympathetic activity, with increased secretion of catecholamine, cortisol, and serotonin can cause oxidative stress, which may damage the arcuate nucleus as well as the hypothalamus and macrophages, and the liver may release pro-inflammatory cytokines. These, in conjunction with an underlying deficiency in long chain PUFA, may damage the arcuate nucleus as well as neuropeptide-Y and pro-opiomelanocortin neurons and insulin receptors in the brain, especially during fetal life, infancy, and childhood, resulting in their dysfunction(32).

33. Elevated 5-HT (serotonin) levels in early postnatal life  and autism spectrum disorders (ASDs)
In the study to examine two inbred mouse strains (C57BL/6 and BALB/c) with respect to these phenomena of transient brain overgrowth in early postnatal life and elevated 5-HT (serotonin) levels in blood platelets (platelet hyperserotonemia). The BALB/c strain is less social and exhibits some other autistic-like behaviors, found that  in mice, autistic-like shifts in the brain and periphery may be associated with less autistic-like behaviors. Importantly, they suggest that consistency among behavioral, anatomical, and physiological measures may expedite the validation of new and previously proposed mouse models of autism, and that the construct validity of models should be demonstrated when these measures are inconsistent(33).

34. Carcinoid Heart Disease and high levels of Serotonin
In the study to review our experience with 604 patients in the Duke Carcinoid Database. Nineteen patients with proven carcinoid heart disease (by cardiac catheterization and/or echocardiogram) were compared with the remaining 585 noncardiac patients in the database with regard to circulating serotonin and its principal metabolite, showed that study reviews our experience with 604 patients in the Duke Carcinoid Database. Nineteen patients with proven carcinoid heart disease (by cardiac catheterization and/or echocardiogram) were compared with the remaining 585 noncardiac patients in the database with regard to circulating serotonin and its principal metabolite(34).

35. Serotonin neurotransmission in anorexia nervosa
Patients with anorexia nervosa (AN) show extreme dieting weight loss, hyperactivity, depression/anxiety, self-control, and behavioral impulsivity. 5-Hydroxytryptamine (5-HT; serotonin) is involved in almost all the behavioral changes observed in AN patients. According to the study by  University of Karachi, Karachi, diet restriction-induced exaggerated feedback control over 5-HT synthesis and the smaller availability of tryptophan decreases serotonin neurotransmission at postsynaptic sites, leading to hyperactivity, depression, and behavioral impulsivity. A compensatory upregulation of postsynaptic 5-HT-1A receptors and hypophagic serotonin receptors may be involved in anxiety and suppression of appetite(35).

36. Obesity, whole blood serotonin and sex differences in healthy volunteers
In the study of healthy adult volunteers (N = 68) who gave whole blood samples for measurement of WB serotonin, and underwent BMI waist circumference (WC) and waist-to-hip ratio (WHR) assessment as well as DEXA (dual energy X-ray absorptiometry) scans for anthropometric parameters, showed that for the whole sample, WB serotonin was significantly negatively correlated with BMI, WC, WHR as well as android, gynoid and total % body fat. Analysis by sex showed significant negative correlations between WB serotonin and android, gynoid as well as total fat in males, but not in females(36).

37. Serotonin and wound healing
The molecule serotonin (5-hydroxytryptamine or 5-HT) is involved in numerous biological processes both inside and outside of the central nervous system. 5-HT signals through 5-HT receptors and it is the diversity of these receptors and their subtypes that give rise to the varied physiological responses. It is clear that platelet derived serotonin is critical for normal wound healing in multiple organs including, liver, lung heart and skin, according to the study by William Leech Building, Newcastle University(37)

38. Tryptophan depletion affects heart rate
In a a randomized, counterbalanced, double-blind crossover design study, nineteen patients in remission from depression received high-dose and low-dose acute tryptophan depletion, found that high-dose acute tryptophan depletion led to a larger increase in depressive symptoms than did low-dose acute tryptophan depletion. High-dose acute tryptophan depletion decreased heart rate variability and increased impulsivity and anxiety, but only in patients with a history of suicidal ideation. Symptom effects of high-dose acute tryptophan depletion correlated with low heart rate variability at baseline(38).

39. Serotonin and insulin resistance
In the study to assess the effect of 5-HT on insulin-mediated glucose uptake, showed that the effects of 5-HT on insulin-mediated glucose uptake were partially reversed by vasodilation with carbachol. In contrast to the results for the hindlimb, 10 microM 5-HT had no significant effect on either basal glucose uptake or the stimulation of glucose uptake mediated by 15 nM insulin by isolated incubated soleus or extensor digitorum longus muscles. It is concluded that 5-HT impairs insulin-mediated glucose uptake in the perfused rat hindlimb that may derive from vascular shunting not apparent when muscles are incubated with 5-HT in vitro(39).

40. Serotonin and type 2 diabetes
In the study of the serotonin 2C receptor (5-HT(2C)R) agonists for their anorectic properties, significantly improve glucose tolerance and reduce plasma insulin in murine models of obesity and type 2 diabetes, found that 5-HT(2C)R agonist-induced improvements in glucose homeostasis occurred at concentrations of agonist that had no effect on ingestive behavior, energy expenditure, locomotor activity, body weight, or fat mass. We determined that this primary effect on glucose homeostasis requires downstream activation of melanocortin-4 receptors (MC4Rs), but not MC3Rs(40).

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Sources
(31) http://www.ncbi.nlm.nih.gov/pubmed/22371656
(32) http://www.ncbi.nlm.nih.gov/pubmed/22913633
(33) http://www.ncbi.nlm.nih.gov/pubmed/22450231
(34) http://circ.ahajournals.org/content/92/4/790.full
(35) http://www.ncbi.nlm.nih.gov/pubmed/22854305
(36) http://www.ncbi.nlm.nih.gov/pubmed/22797367
(37) http://www.ncbi.nlm.nih.gov/pubmed/23032152
(38) http://www.ncbi.nlm.nih.gov/pubmed/16603135
(39) http://www.ncbi.nlm.nih.gov/pubmed?term=serotonin%20and%20%20insulin%20resistance
(40) http://www.ncbi.nlm.nih.gov/pubmed/17983585