Hormones: December 2012

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.
1. Brain serotonin, carbohydrate-craving, obesity and depression
Serotonin-releasing brain neurons are unique in that the amount of neurotransmitter they release is normally controlled by food intake, according to the study by Massachusetts Institute of Technology, Cambridge serotonin release is also involved in such functions as sleep onset, pain sensitivity, blood pressure regulation, and control of the mood. Hence many patients learn to overeat carbohydrates (particularly snack foods, like potato chips or pastries, which are rich in carbohydrates and fats) to make themselves feel better. This tendency to use certain foods as though they were drugs is a frequent cause of weight gain, and can also be seen in patients who become fat when exposed to stress, or in women with premenstrual syndrome, or in patients with "winter depression," or in people who are attempting to give up smoking. (Nicotine, like dietary carbohydrates, increases brain serotonin secretion; nicotine withdrawal has the opposite effect.) It also occurs in patients with normal-weight bulimia. Dexfenfluramine constitutes a highly effective treatment for such patients. In addition to producing its general satiety-promoting effect, it specifically reduces their overconsumption of carbohydrate-rich (or carbohydrate-and fat-rich) foods(1).

2. Brain serotonin in excessive carbohydrate snacking craving
Brain neurotransmitter serotonin plays an essential role in a specific hunger for carbohydrate-rich foods in animals and human beings, researchers found that consumption of a carbohydrate-rich meal increases the synthesis and release of brain serotonin (by enhancing the brain uptake of its precursor, tryptophan). As a consequence of this increased release of serotonin, carbohydrate intake is decreased at the next meal. Consumption of protein does not increase brain serotonin levels or decrease carbohydrate intake. A subgroup of obese individuals who consume carbohydrate-rich snack foods at specific times of day or evening has been identified. Such individuals do not routinely snack on protein-rich foods, and their consumption of calories and nutrients at meals is not excessive. Evidence is presented that carbohydrate snacking seems to be related to a "need" to increase the level of brain serotonin; treatment with a drug, d-1 fenfluramine, that increases serotoninergic neurotransmission significantly decreases carbohydrate snack consumption. Weight loss among the population of carbohydrate cravers might be most successful if treatment includes either a diet or drugs that increase brain serotonin activity when the need to snack on carbohydrate is most likely to occur(2).

3. Changes in mood after carbohydrate consumption
In the study to identify two groups of obese individuals who consume excessive calories primarily as snack foods, found that using standardized self-report questionnaires, we measured mood before and 2 h after consumption of a high-carbohydrate lunch (104 g CHO). Responses to the meal differed significantly: noncarbohydrate cravers reported feeling considerably less alert, more fatigued and sleepy, while carbohydrate cravers described little or no change in these aspects of mood.(3)

4. Mood and carbohydrate cravings
In the study to investigate a sample of 113 males and 138 female college students of the relationship between mood and carbohydrate cravings, and the possible role of gender in these associations, found that individuals classifying themselves as "carbohydrate cravers" reported foods rich in carbohydrates, and "protein cravers" reported protein-rich foods as being the ones they most strongly craved. Carbohydrate cravers reported feeling distressed prior to their cravings and satisfied, happy/good and relaxed following carbohydrate consumption. Protein cravers reported feeling anxious or hungry prior to their cravings and happy, normal, bored, and energetic following protein-rich food consumption(4).

5. Effects of protein and carbohydrate meals on mood and performance: interactions with sex and age
In the study to investigate the normal adult subjects (n = 184) consumed a high-protein or high-carbohydrate meal and were tested two hours later their mood and performance, found that females, but not males, reported greater sleepiness after a carbohydrate as opposed to a protein meal. Male subjects, but not females, reported greater calmness after a carbohydrate as opposed to a protein meal. When meals were eaten for breakfast (but not for lunch) individuals 40 yr of age or older felt more tense and less calm after a protein than after a carbohydrate meal. Although older subjects reported subjective discomfort after a morning protein meal, they displayed objective performance impairments after a carbohydrate lunch. Subjects 40 yr of age or older were impaired on a test of sustained selective attention (dichotic shadowing) after consuming a high-carbohydrate lunch(5).

6. Mood, performance, and pain sensitivity: changes induced by food constituents
In the study to examine the behavioral effects of the dietary constituents tryptophan and tyrosine on human mood, sensorimotor performance and pain sensitivity, found that tryptophan and tyrosine are neurotransmitter precursors present in varying amount in protein-containing foods. Tryptophan (50 mg/kg) increased subjective drowsiness and fatigue but unlike many hypnotics did not impair sensorimotor performance. Tryptophan also decreased human pain sensitivity in a manner that was more specific than certain analgesic drugs(6).

7. Effects of dietary neurotransmitter precursors on human behavior
In a double-blind, crossover study the possible effects of tryptophan and tyrosine on human behavior, single oral doses of these substances and matched placebos were administered to 20 men, found that
tryptophan increased subjective fatigue and decreased self-ratings of vigor and alertness, but did not impair performance on any of the tests. Tyrosine produced no effects in our young population compared with placebo, but did decrease reaction time relative to tryptophan. It may be concluded that tryptophan has significant sedative-like properties, but unlike other sedatives may not impair performance(7).

8. Serotonin: influences on male sexual behavior
Serotonin (5-HT) is primarily inhibitory, although stimulation of 5-HT(2C) receptors increases erections and inhibits ejaculation, whereas stimulation of 5-HT(1A) receptors has the opposite effects: facilitation of ejaculation and, in some circumstances, inhibition of erection. 5-HT is released in the anterior lateral hypothalamus at the time of ejaculation. Microinjections of selective serotonin reuptake inhibitors there delay the onset of copulation and delay ejaculation after copulation begins, according to the study by State University of New York(8).

9. Neuroactive steroid effects on cognitive functions with a focus on the serotonin and GABA systems
In the study to review the neuroactive steroid effects on serotonin and GABA systems, along with the subsequent effects on cognitive functions, showed that Estrogen alone, or in combination with progesterone, affects the brain serotonin system differently in different parts of the brain, which can at least partly explain the opposite effects on mood of those hormones. Many of the progesterone effects in the brain are mediated by its metabolite allopregnanolone. Allopregnanolone, by changing GABA(A) receptor expression or sensitivity, is involved in premenstrual mood changes; and it also induces cognitive deficits, such as spatial-learning impairment(9).

10. Serotonin, aging and cognitive functions
Serotonin and acetylcholine interact to allow normal cognitive functions in the brain. Thus, a partial reduction in both cholinergic and serotonergic functions will cause severe memory impairment in young as well as in aged rats, according to the dtudy by Department of Neurobiology, Weizmann Institute(10).

11. Serotonin circuits and anxiety
Fear, a reaction to a threatening situation, is a broadly adaptive feature crucial to the survival and reproductive fitness of individual organisms. By contrast, anxiety is an inappropriate behavioral response often to a perceived, not real, threat. In the study by The Salk Institute for Biological Studies functional imaging, biochemical analysis, and lesion studies with humans have identified the HPA axis and the amygdala as key neuroanatomical regions driving both fear and anxiety. Abnormalities in these biological systems lead to misregulated fear and anxiety behaviors such as panic attacks and post-traumatic stress disorders. These behaviors are often treated by increasing serotonin levels at synapses, suggesting a role for serotonin signaling in ameliorating both fear and anxiety. Interestingly, serotonin signaling is highly conserved between mammals and invertebrates(11).

12. Serotonin in Alzheimer's disease
Mounting evidence accumulated over the past few years indicates that the neurotransmitter serotonin plays a significant role in cognition. In the study by Northeast Ohio Medical University researchers indicated that as a drug target, serotonin receptors have received notable attention due in particular to the role of several serotonin-receptor subclasses in cognition and memory. The intimate anatomical and neurochemical association of the serotonergic system with brain areas that regulate memory and learning has directed current drug discovery programmes to focus on this system as a major therapeutic drug target. While many of these compounds will likely find application as adjuvant therapy in the symptomatic treatment of Alzheimer's disease, there are currently only a few drug entities with activity against serotonin receptors that may offer the potential to alter the progression of the disease(12).

13. Biosynthesis and the development of Parkinson's disease and schizophrenia

In the study of Somatic transposition in the brain influences the biosynthesis of metabolites involved in Parkinson's disease and schizophrenia, researcher shows that somatic transposition in the human brain can influence the biosynthesis of more than 250 metabolites, including dopamine, serotonin and glutamate, shows large inter-individual variability in metabolic effects, and may contribute to the development of Parkinson's disease and schizophrenia.

14. Serotonin and vasoconstrictor synergism
In the study to observe the Contractile synergism between serotonin (5-hydroxytryptamine, 5-HT) and other vasoconstrictor substances in a number of peripheral and cerebrovascular blood vessels, found that this phenomenon may play an important role in certain pathological states such as hypertension, peripheral vascular disease, and coronary spasm. Tthe synergism between serotonin and other vasoconstrictor agents and focus on a recently described type of vasoconstrictor synergism in which precontraction with a non-5-HT receptor agonist yields an enhanced contractile response to serotonin which is mediated by previously inactive or "silent" 5-HT receptor subtypes(14).

15. Serotonin and arterial vessels
The vasodilator effects of serotonin can be caused by (a) inhibiting vascular smooth muscle directly, (b) releasing other inhibitory substances, such as vasoactive intestinal polypeptide, (c) inhibiting adrenergic neurotransmission, and (d) triggering of endothelium-dependent relaxation, according to the study by J Cardiovasc Pharmacol. 1984;6 Suppl 2:S421-8(15).

16. Serotonin and vascular reactivity
In the study of Serotonin causes of contraction of the vascular smooth muscle cells in most blood vessel, found that at low concentrations serotonin amplifies the vasoconstrictor responses to other vasoactive substances. Ultimately the effect of serotonin on vascular constriction is defined by the balance between these different actions. In the intact organism under normal conditions serotonin may play a modulatory role but exacerbation of the contractile effects because of hypersensitivity of the smooth muscle cells, local physical or humoral factors or loss of the relaxatory ability may lead to abnormal tissue responses. Thus, serotonin-induced vasoconstrictor responses may play a role in the etiology of vasospasm and peripheral vascular diseases, in particular at sites of endothelial lesions(16).

17. Serotonin and the blood vessel wall
Serotonin has complex effects on the cardiovascular system. In the intact animal it may cause increases or decreases of blood pressure and in isolated blood vessels contraction or relaxation depending on the species and vascular bed studied, the route of administration and the dosage used. According to the study by Dr. Vanhoutte PM and Dr. Lüscher TF. serotonin may act indirectly by amplifying the response to norepinephrine and other agonists, by displacing norepinephrine from adrenergic nerve terminals or releasing constrictor substance(s) from the endothelium. Dilatation in response to serotonin is mediated by endothelial and prejunctional S1-serotonergic receptors which pharmacologically resemble 5-HT1-binding sites. In hypertension, constrictor responses to serotonin are augmented, while the vasodilator effects of the monoamine are decreased. The constrictor response to serotonin is increased more than those to other agonists, suggesting a functional rather than a structural adaptation of the hypertensive blood vessel wall. In hypertension the turnover of circulating platelets, the major source of peripheral serotonin, is accelerated and the mechanisms for the removal of the monoamine are impaired. The functional changes of the blood vessel wall and platelets could play a role in the maintenance of the increased peripheral vascular resistance in chronic hypertension, and they could be involved in the pathogenesis of complications of the hypertensive process(17).

18. Cardiovascular effects of serotonin
Serotonin causes contraction of most large arteries and veins; it also causes contraction of venules. This is due mainly to direct activation of vascular smooth muscle, although amplification of the response to other endogenous vasoconstrictors (e.g., angiotensin II and norepinephrine) as well as facilitated release of norepinephrine may contribute. In peripheral blood vessels, the receptors mediating the contractions evoked by serotonin belong mainly to the 5-HT2-serotonergic subtype; in the coronary and cerebral arteries, this need not be the case. Vasodilator responses to serotonin are seen mainly at the arteriolar level, but they can also be observed in larger blood vessels. They can be caused by the release of other endogenous vasodilators (e.g., vasoactive intestinal polypeptide), direct relaxation of vascular smooth muscle, inhibition of adrenergic neurotransmission, or production of endothelium-derived relaxing factor(s). The dilator responses to serotonin are mediated by receptors with characteristics similar to 5-HT1-serotonergic binding sites. Aggregating platelets release enough serotonin to evoke both constrictor and dilator responses. The absence of endothelium may change the primary response to aggregating platelets from relaxation to contraction. The responsiveness of the blood vessel wall to serotonin can be augmented acutely by local hypoxia or by cooling(18).

19. Correction of altered serotonin exchange in adolescents with functional disorders of digestive system
In the searching for the ways of improvement treatment of functional pathologies of the system of digestion an author is studied the concentration and the role of serotonin in 180 adolescents, showed that serotonin receptors 5HT1 agonists were used for patients with paroxysms of abdominal pain mainly at neurocirculatory disfunction and migraine(19).

20. Serotonin and Fibromyalgia and migraine
In the study of fibromyalgia sufferers randomly administered a combination of monoamine-oxidase inhibitors (MAOIs)-A/B with 5-HTP, 5-HTP alone, MAOIs-A/B alone, or the tricyclic drug amitriptyline in order to compare the efficacy of these treatments, showed that high prevalence of migraine in the population of fibromyalgia sufferers, suggests a common ground shared by fibromyalgia and migraine. Migraine has been demonstrated to be characterized by a defect in the serotonergic and adrenergic systems. A parallel dramatic failure of serotonergic systems and a defect of adrenergic transmission have been evidenced to affect fibromyalgia sufferers too. Enhancing serotonergic analgesia while increasing adrenergically mediated analgesia seems to be an important tool in fibromyalgia(20).

21. Serotonin in the regulation of emotion processing and mood
Monoamines, such as serotonin, dopamine, and norepinephrine, play a crucial role in the regulation of emotion processing and mood. In the study to investigate how polymorphisms of the serotonin transporter (5-HTT) and catechol-O-methyltransferase (COMT) influence emotion recognition abilities, researchers at the Department of General Psychiatry, Innsbruck Medical University, found that s-allele carriers performed significantly worse in the recognition of happy faces, but did better in the recognition of fearful faces, compared with homozygous l-carriers of the 5-HTT gene. Neither 5-HTT nor COMT genotypes influenced the ability to discriminate between different intensities of sadness or happiness on the PEAT(21).

22. Hemostasis, platelet function and serotonin in acute and chronic renal failure
In the study to investigate some fibrinolytic parameters and platelet function of 17 patients with ARF and compared to healthy volunteers and subjects with chronic renal failure (CRF), found that since serotonin may participate in pathological processes resulting from platelet/vessel wall interactions, its level in the whole blood and plasma was also assayed. In ARF and CRF platelet aggregatory responses in both whole blood and in platelet rich plasma upon stimulation with various agonists (collagen, arachidonic acid, ADP, ristocetin) were lower than those obtained in healthy volunteers. Serotonin uptake and its release from platelets were markedly diminished in patients with ARF and CRF. Chronic renal failure exhibit a slightly different pattern of coagulopathies that acute renal failure(22).

23. Platelet functions, some hemostatic and fibrinolytic parameters in relation to serotonin
Erythropoietin corrects anemia and improves hemostasis, but on the other hand bears a risk of thrombotic complications. In the study to evaluate bleeding time, platelet functions and some hemostatic and fibrinolytic parameters in relation to blood and platelet serotonin before and after 1, 2, 4, 8 and 12 weeks of treatment in 22 chronically hemodialyzed patients were administered with human recombinant erythropoietin (rHuEPO) in a dose of 2000 IU s.c. 3 times a week, showed that rHuEPO may improve platelet/vessel wall interactions possibly by means of serotonergic mechanisms. A lowered activity of inhibitors of fibrinolysis may be regarded as a protection against a general tendency to thrombosis during rHuEPO therapy(23).

24. Serotonin and carcinoid
There is a report of a 66-year-old woman was diagnosed with hepatic metastasized carcinoid tumor of the ileocecal junction resulting in elevated plasma chromogranin A levels and urinary 5-hydroxyindoleacetic acid (5-HIAA) levels. Further examination showed right-sided heart failure with severe tricuspid valve regurgitation. Carcinoid tumors produce serotonin which leads to flushing, secretory diarrhea, bronchospasm and hypotension, known as carcinoid syndrome. Serotonin is metabolized to 5-HIAA, which is inactive, in the liver and the lungs(24).

25. Serotonin and Substance abuse
Serotonin (5-hydroxytryptamine [5-HT]) is an important neurotransmitter implicated in regulating substance-use disorder (SUD) acquisition, maintenance, and recovery. According to the VA Connecticut Healthcare/Yale University School of Medicine, During the past several years, an abundance of research has begun discovering and describing specific 5-HT genetic polymorphisms associated with SUDs. Genetic variations in the 5-HT system, such as SLC6A4, HTR1B, HTR2A, HTR2C, HTR3 (HTR3A, HTR3B, HTR3C, HTR3D, and HTR3E), likely play a role contributing to SUD patient heterogeneity(25).

26. Serotonin and the severity of alcohol drinking
Severe drinking can cause serious morbidity and death. In a double-blind controlled trial randomized 283 alcoholics by genotype in the 5'-regulatory region of the 5-HTT gene (LL/LS/SS), with additional genotyping for another functional single-nucleotide polymorphism (T/G), rs1042173, in the 3'-untranslated region, showed that Individuals with the LL genotype who received ondansetron had a lower mean number of drinks per drinking day (-1.62) and a higher percentage of days abstinent (11.27%) than those who received placebo. Among ondansetron recipients, the number of drinks per drinking day was lower (-1.53) and the percentage of days abstinent higher (9.73%) in LL compared with LS/SS individuals. LL individuals in the ondansetron group also had a lower number of drinks per drinking day (-1.45) and a higher percentage of days abstinent (9.65%) than all other genotype and treatment groups combined. For both number of drinks per drinking day and percentage of days abstinent, 5'-HTTLPR and rs1042173 variants interacted significantly. LL/TT individuals in the ondansetron group had a lower number of drinks per drinking day (-2.63) and a higher percentage of days abstinent (16.99%) than all other genotype and treatment groups combined(26).

27. Serotonin and Autism
Autism is a complex neurodevelopmental disorder characterized by impaired reciprocal social interaction, communication deficits and repetitive behaviors. In the study to test the hypothesis that serotonin dysfunction can contribute to the core symptoms of autism, by analyzing mice lacking brain serotonin (via a null mutation in the gene for tryptophan hydroxylase 2 (TPH2)) for behaviors that are relevant to this disorder, found that mice lacking brain serotonin (TPH2-/-) showed substantial deficits in numerous validated tests of social interaction and communication. These mice also display highly repetitive and compulsive behaviors. Newborn TPH2-/- mutant mice show delays in the expression of key developmental milestones and their diminished preference for maternal scents over the scent of an unrelated female is a forerunner of more severe socialization deficits that emerge in weanlings and persist into adulthood. Taken together, these results indicate that a hypo-serotonin condition can lead to behavioral traits that are highly characteristic of autism(27).

28. Serotonin and severity of attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) symptoms.
In the study to examine the association between a common serotonin transporter gene (SLC6A4) polymorphism 5-HTTLPR/rs25531 with severity of attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) symptoms, researchers at the Department of Psychiatry and Behavioral Sciences, Stony Brook University, showed that the 5-HTTLPR/rs25531 polymorphism or its correlates may modulate severity of ADHD and ASD symptoms in children with ASD, but in different ways. These tentative, hypothesis-generating findings require replication with larger independent samples(28).

29. Serotonin and sexual desire disorders
Hypoactive sexual desire disorder (HSDD) is thought to be the most prevalent form of female sexual dysfunction (FSD), affecting up to 1 in 10 US women. Hypoactive sexual desire disorder is defined by the Diagnostic and Statistical Manual of Mental Disorders, showed that Causes of low desire include chronic medical conditions, medications, surgeries, and psychosocial factors, but not necessarily increased age; both pre- and postmenopausal women can have HSDD, although the frequency appears to vary by age. Sexual function requires the complex interaction of multiple neurotransmitters and hormones, both centrally and peripherally, and sexual desire is considered the result of a complex balance between inhibitory and excitatory pathways in the brain. For example, dopamine, estrogen, progesterone, and testosterone play an excitatory role, whereas serotonin and prolactin are inhibitory. Thus, decreased sexual desire could be due to a reduced level of excitatory activity, an increased level of inhibitory activity, or both. A number of validated self-report and clinician-administered instruments are available for assessing female sexual function; however, most have been used primarily in clinical research trials(29).

30. Monoamine deficiency and relative nutritional deficiency
In the study to to demonstrate that the primary component of chronic centrally acting monoamine (serotonin, dopamine, norepinephrine, and epinephrine) disease is a relative nutritional deficiency induced by postsynaptic neuron damage, showed that humans suffering from chronic centrally acting monoamine-related disease are not suffering from a drug deficiency; they are suffering from a relative nutritional deficiency involving serotonin and dopamine amino acid precursors. Whenever low or inadequate levels of monoamine neurotransmitters exist, a relative nutritional deficiency is present. These precursors must be administered simultaneously under the guidance of monoamine transporter optimization in order to achieve optimal relative nutritional deficiency management. Improper administration of these precursors can exacerbate and/or facilitate new onset of centrally acting monoamine-related relative nutritional deficiencies(30).

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).

41. Serotonin and irritable bowel syndrome with diarrhea
In a biopsy specimens evaluation to assess the inflammation, enterochromaffin cell numbers, 5-HT content, and messenger RNA (mRNA) levels for the synthetic enzyme, tryptophan hydroxylase 1, and the serotonin transporter (SERT) by quantitative real-time reverse-transcription polymerase chain reaction, indicated that the role of 5-HT signaling in IBS in children and argue against such a role in FD(41).

42. 5-HT(1A) receptors and lower urinary tract function and 'fight-or-flight' conditions
In the study to examine the role of 5-HT(1A) receptors in control of lower urinary tract function in cats, using 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) as agonists and WAY100635 and LY206130 as antagonists, found that 5-HT(1A) receptor stimulation is inhibitory to bladder function in cats, especially under conditions where the bladder is hyperactive due to irritation. Furthermore, these bladder-inhibitory effects are the exact opposite of the bladder-excitatory effects of 8-OH-DPAT reported in rats. 5-HT(1A) receptor stimulation increases EUS motoneuron activity when driven by nociceptive bladder afferent inputs but not when driven by non-nociceptive afferent inputs. In summary, 5-HT(1A) receptor agonists facilitate a nociceptor-driven spinal reflex (sphincter activity) but inhibit a nociceptor-driven supraspinal reflex (micturition). This pattern of activity would facilitate urine storage and may be important under 'fight-or-flight' conditions when serotonergic activity is high(42).

43. Neuronal serotonin regulates growth of the intestinal mucosa
5-HT promotes growth and turnover of the intestinal mucosal epithelium. Surprisingly, these processes appear to be mediated by neuronal, rather than mucosal, 5-HT. The 5-HT(2A) receptor activates cholinergic neurons, which provide a muscarinic innervation to epithelial effectors, according to teh study by College of Physicians and Surgeons, Columbia University(43)

44. Serotonin and reproduction
Serotonin, a biogenic amine, is present in significant amounts in many structures of the CNS. It is involved in regulation of a wide variety of physiological functions, such as sensory and motor functions, memory, mood, and secretion of hormones including reproductive hormones. In the study of oral administration to female CD rats (20/group) at doses of 0, 3, 10, or 30 mg/kg to evaluate effects on mating, fertility, litter size, live birth index (100 x total liveborn progeny/litter size), progeny survival, and weight gain of each litter, found that on postpartum day 8, progeny in the control, 30 mg/kg and 30 mg/kg recovery groups were removed from dams for 4 h. Progeny were weighed as litters, returned to the dams for a 1-h nursing period, and then weighed again to provide an indication of milk intake. Mating and fertility, using the present study design, were not affected by treatment with amesergide. No effects were observed on litter size, live birth index, or progeny survival. In contrast, treatment with amesergide throughout gestation and lactation produced a significant dose-related depression in progeny body weight gains(44).

45. Serotonin and aging
In the study to assess Serotonin (5-HT) neuron and neurotransmitter loss in normal aging and neuropsychiatric diseases of late life and its contribution to behavioral changes commonly observed in the elderly population, found that there is also increasing evidence that a combination of disturbances in cholinergic and serotonergic function may play a role in cognitive impairment in Alzheimer's disease (AD), with serotonergic dysfunction potentially responsible for a significant portion of the behavioral aspects of the disease. This implication of the 5-HT system in aging and age-related cognitive and mood disorders rests in large part on post mortem studies and animal models, which are limited in their capacity to predict dynamic human biochemical-behavior relationships or to accurately model the living human brain. Initial applications of functional brain imaging with positron emission tomography (PET) in the in vivo study of the brain in aging depression, and dementia focused on characterizing alterations in physiological measurements of cerebral metabolism and perfusion. However, recent advances in PET radiochemistry, instrumentation, and image processing have paved the way for noninvasive means to test specific hypotheses regarding the direct involvement of 5-HT neurons in the behavioral features of aging and to define and monitor therapeutic regimens for neuropsychiatric conditions of late life(45).

46. The role of serotonin in the regulation of bone metabolism

In the brain, brain derived serotonin regulates bone mass through sympathetic nervous system. In addition, inhibition of GDS biosynthesis can treat osteoporosis in ovariectomized rodents by increasing bone formation. The emerging evidence has suggested that inhibiting GDS biosynthesis could become a new anabolic treatment for osteoporosis in humans, according to thye study by Department of Genetics and Development, Columbia University(46).

47. N-acetyl serotonin and neuroprotectants for retinas
N-acetylserotonin (NAS) is synthesized from serotonin by arylalkylamine N-acetyltransferase (AANAT), which is predominantly expressed in the pineal gland and retina. Researchers at the Emory University School of Medicine, found that he compound N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3-carboxamide (HIOC) selectively activates TrkB receptor with greater potency than NAS. It potently protects retinas from light-induced retinal degeneration (LIRD), which is tightly coupled with pronounced TrkB activation in retinas. Pharmacokinetic studies demonstrate that this compound is stable in serum and liver microsomes. It can pass the blood-brain barrier and blood-retinal barrier. Hence, HIOC is a good lead compound for further drug development for treating retinal degenerative diseases(47).

48. Serotonin and inflammatory pain
In the study to investigate the reverse transcriptase polymerase chain reaction (RT-PCR) technique used to examine the changes of the expression of 5-hydroxytryptamine (5-HT) receptors in the rat lumbar dorsal root ganglion (DRG) following subcutaneous bee venom (BV) injection into the plantar surface of the unilateral hindpaw, showed that the different sets of 5-HT receptor subtypes work at different stages of the inflammatory pain induced by subcutaneous BV injection(48).

49. Serotonin and life span
In the study to develop a new quantitative method to analyze Caenorhabditis elegans behavioral states, found that the proportion of time spent in each state is modulated by past nutritional experiences of the animal. This two-state behavior is regulated through serotonin as well as insulin and TGF-beta signaling pathways. Biogenic amines signaling could allow the worm to adapt to fast changes in the environment when peptide transcriptional pathways may mediate slower adaptive changes(49).

50. Fetal serotonin signaling: setting pathways for early childhood development and behavior
Finely tuning levels of the key neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) during early life is essential for brain development and setting pathways for health and disorder across the early life span. Understanding the impact of early changes in serotonergic programming offers critical insights that might explain patterns of individual differences in developmental risk and resilience, according to the study by Child and Family Research Institute(50).

Tuesday, December 4, 2012

Serotonin