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Role of Serotonin in Health and Diseases

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 7034

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Prof. Dr. Tomasz Popławski

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Department of Microbiology and Pharmaceutical Biochemistry, Medical University of Lodz, 90-136 Lodz, Poland
Interests: DNA; epigenetics; genetic analysis; cyto and genotoxicity; biochemistry; enzymes; metabolism
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Dear Colleagues,

It is commonly agreed that a decreased serotonergic function is involved in the onset and progression of depression. However, serotonin is involved in many physiological functions and behavioral processes, including mood, appetite, sleep, activity, suicide, sexual behavior, and cognition; and all of them can be affected in depression. The great majority of serotonin (up to 90%) is produced and metabolized in the digestive tract and the rest in the nervous system. It is synthesized in the gastrointestinal tract by enterochromaffin cells, mast cells, lymphocytes, and intestinal bacteria with the involvement of tryptophan (TRP) hydroxylase 1 (TPH-1) and in the central nervous system, with the involvement of TPH-2. Approximately 5% of TRP is metabolized in the serotonin pathway and the rest in the kynurenine pathway with the involvement of indole 2,3-dioxygenases (IDO-1 and IDO-2). In recent years, we witnessed dramatic progress that has substantially enhanced our understanding of the functions of 5-HT and the underlying molecular, cellular, physiological, and circuit mechanisms. Here, we propose to invite leading experts on 5-HT research to review their findings, ranging from its development to its role in regulating human health.

Prof. Dr. Tomasz Popławski
Guest Editor

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14 pages, 2054 KiB

Open AccessArticle

Kappa Opioid Receptors Reduce Serotonin Uptake and Escitalopram Efficacy in the Mouse Substantia Nigra Pars Reticulata

by Alyssa M. West, Katherine M. Holleran and Sara R. Jones

Int. J. Mol. Sci. 2023, 24(3), 2080; https://doi.org/10.3390/ijms24032080 - 20 Jan 2023

Cited by 3 | Viewed by 1789

Abstract

The serotonin and kappa opioid receptor (KOR) systems are strongly implicated in disorders of negative affect, such as anxiety and depression. KORs expressed on axon terminals inhibit the release of neurotransmitters, including serotonin. The substantia nigra pars reticulata (SNr) is involved in regulating affective behaviors. It receives the densest serotonergic innervation in the brain and has high KOR expression; however, the influence of KORs on serotonin transmission in this region is yet to be explored. Here, we used ex vivo fast-scan cyclic voltammetry (FSCV) to investigate the effects of a KOR agonist, U50, 488 (U50), and a selective serotonin reuptake inhibitor, escitalopram, on serotonin release and reuptake in the SNr. U50 alone reduced serotonin release and uptake, and escitalopram alone augmented serotonin release and slowed reuptake, while pretreatment with U50 blunted both the release and uptake effects of escitalopram. Here, we show that the KOR influences serotonin signaling in the SNr in multiple ways and short-term activation of the KOR alters serotonin responses to escitalopram. These interactions between KORs and serotonin may contribute to the complexity in the responses to treatments for disorders of negative affect. Ultimately, the KOR system may prove to be a promising pharmacological target, alongside traditional antidepressant treatments. Full article

(This article belongs to the Special Issue Role of Serotonin in Health and Diseases)

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15 pages, 1699 KiB

Open AccessArticle

Renal Sympathetic Hyperactivity in Diabetes Is Modulated by 5-HT_1D Receptor Activation via NO Pathway

by Juan Francisco Fernández-González, José Ángel García-Pedraza, José Luis Ordóñez, Anaïs Clara Terol-Úbeda, María Luisa Martín, Asunción Morán and Mónica García-Domingo

Int. J. Mol. Sci. 2023, 24(2), 1378; https://doi.org/10.3390/ijms24021378 - 10 Jan 2023

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Abstract

Renal vasculature, which is highly innervated by sympathetic fibers, contributes to cardiovascular homeostasis. This renal sympathetic outflow is inhibited by 5-HT in normoglycaemic rats. Considering that diabetes induces cardiovascular complications, we aimed to determine whether diabetic state modifies noradrenergic input at renal level and its serotonergic modulation in rats. Alloxan diabetic rats were anaesthetized (pentobarbital; 60 mg/kg i.p.) and prepared for in situ autoperfusion of the left kidney to continuously measure systemic blood pressure (SBP), heart rate (HR), and renal perfusion pressure (RPP). Electrical stimulation of renal sympathetic outflow induces frequency-dependent increases (Δ) in RPP (23.9 ± 2.1, 59.5 ± 1.9, and 80.5 ± 3.5 mm Hg at 2, 4, and 6 Hz, respectively), which were higher than in normoglycaemic rats, without modifying HR or SBP. Intraarterial bolus of 5-HT and 5-CT (5-HT_1/5/7 agonist) reduced electrically induced ΔRPP. Only L-694,247 (5-HT_1D agonist) reproduced 5-CT inhibition on sympathetic-induced vasoconstrictions, whereas it did not modify exogenous noradrenaline-induced ΔRPP. 5-CT inhibition was exclusively abolished by i.v. bolus of LY310762 (5-HT_1D antagonist). An inhibitor of guanylyl cyclase, ODQ (i.v.), completely reversed the L-694,247 inhibitory effect. In conclusion, diabetes induces an enhancement in sympathetic-induced vasopressor responses at the renal level. Prejunctional 5-HT_1D receptors, via the nitric oxide pathway, inhibit noradrenergic-induced vasoconstrictions in diabetic rats. Full article

(This article belongs to the Special Issue Role of Serotonin in Health and Diseases)

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9 pages, 544 KiB

Open AccessArticle

A Reduced Tryptophan Diet in Patients with Diarrhoea-Predominant Irritable Bowel Syndrome Improves Their Abdominal Symptoms and Their Quality of Life through Reduction of Serotonin Levels and Its Urinary Metabolites

by Cezary Chojnacki, Marta Medrek-Socha, Aleksandra Blonska, Radoslaw Zajdel, Jan Chojnacki and Tomasz Poplawski

Int. J. Mol. Sci. 2022, 23(23), 15314; https://doi.org/10.3390/ijms232315314 - 05 Dec 2022

Cited by 4 | Viewed by 1935

Abstract

(1). An essential component of any treatment for patients with irritable bowel syndrome (IBS) is an adequate diet. Currently, a low FODMAP diet is recommended as a first-line therapy, but it does not relieve abdominal discomfort in all patients, and alternative nutritional treatment is required. The purpose of this study was to evaluate the effect of a tryptophan-lowering diet (TRP) on abdominal and mental symptoms in patients with irritable bowel syndrome with predominant diarrhea (IBS-D). (2). The study included 40 patients with IBS-D, and 40 healthy subjects served as a baseline for IBS-D patients, after excluding comorbidities. The TRP intake was calculated using the nutritional calculator. The severity of abdominal symptoms was assessed using the gastrointestinal symptom rating scale (GSRS-IBS). Mental state was assessed using the Hamilton anxiety rating scale (HAM-A), the Hamilton depression rating scale (HAM-D), and the insomnia severity index (ISI). The serum levels of serotonin and melatonin and the urinary excretion of their metabolites 5-hydroxyindoleacetic acid (5-HIAA) and 6-sulfatoxymelatonin (aMT6) were determined by the ELISA method. The severity of symptoms and laboratory data were analyzed before and after a 12 week diet with tryptophan restricted to a daily dose 10 mg per kilogram body weight. (3). Compared to the control group, patients with IBS-D had a higher serum level of serotonin (198.2 ± 38.1 vs. 142.3 ± 36.4 ng/mL; p < 0.001) but a similar level of melatonin (8.6 ± 1.1 vs. 9.4 ± 3.0 pg/mL; p > 0.05). The urinary excretion of 5-HIAA was also higher in patients with IBS-D patients (7.7 ± 1.5 vs. 6.0 ± 1.7 mg/24 h; p < 0.001). After nutritional treatment, both the serum serotonin level and the urinary 5-HIAA excretion significantly decreased (p < 0.001). The severity of the abdominal symptoms and anxiety also decreased, while the HAM-D score and the ISI score remained unchanged (4). Lowering the dietary intake of tryptophan may reduce abdominal complaints and does not alter the mental state of IBS-D patients. Full article

(This article belongs to the Special Issue Role of Serotonin in Health and Diseases)

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11 pages, 2232 KiB

Open AccessArticle

Uptake and Metabolization of Serotonin by Granulosa Cells Form a Functional Barrier in the Mouse Ovary

by Nina M. Alyoshina, Maria D. Tkachenko, Lyudmila A. Malchenko, Yuri B. Shmukler and Denis A. Nikishin

Int. J. Mol. Sci. 2022, 23(23), 14828; https://doi.org/10.3390/ijms232314828 - 27 Nov 2022

Cited by 5 | Viewed by 1509

Abstract

Serotonin (5-HT) plays an essential role in regulating female reproductive function in many animals. 5-HT accumulates in the mammalian ovary with the involvement of membrane serotonin transporter SERT and is functionally active in the oocytes of growing follicles, but shows almost no activity in follicular cells. In this study, we clarified the interplay between 5-HT membrane transport and its degradation by monoamine oxidase (MAO) in the mammalian ovary. Using pharmacologic agents and immunohistochemical staining of the cryosections of ovaries after serotonin administration in vitro, we demonstrated the activity of transport and degradation systems in ovarian follicles. The MAO inhibitor pargyline increased serotonin accumulation in the granulosa cells of growing follicles, indicating the activity of both serotonin uptake and degradation by MAO in these cells. The activity of MAO and the specificity of the membrane transport of serotonin was confirmed in primary granulosa cell culture treated with pargyline and fluoxetine. Moreover, the accumulation of serotonin is more effective in the denuded oocytes and occurs at lower concentrations than in the oocytes within the follicles. This confirms that the activity of SERT and MAO in the granulosa cells surrounding the oocytes impedes the accumulation of serotonin in the oocytes and forms a functional barrier to serotonin. Full article

(This article belongs to the Special Issue Role of Serotonin in Health and Diseases)

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