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
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