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

Deadline for manuscript submissions: 29 May 2025 | Viewed by 10778

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Special Issue Editor

Dr. Elena E. Voronezhskaya

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Guest Editor

Koltsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow 119334, Russia
Interests: development; neurogenesis; ciliogenesis; serotonylation; invertebrates

Special Issue Information

Dear Colleagues,

What do you imagine when you hear the word "serotonin"? Probably the brain, neurons, mammalian behavior, and migraines. However, serotonin is much more! This biogenic amine (5-hydroxytryptamine, 5- HT) is an ancient substance with a wide variety of functions. It is found in almost all representatives of the animal kingdom, appears in development as early as the single-cell stage, and accompanies the life of the organism until its last days. Normally, serotonin exerts its physiological effects through the activation of more than 14 different receptors on the cell membrane. In addition, it has recently been found that 5-HT as an intracellular agent causes posttranslational protein modification—serotonylation—and is thus involved in important physiological and pathophysiological processes, including permissive gene expression.

In this Special Issue, we would like to encourage all researchers whose work is related to serotonin to present their latest findings, in-depth expertise, and methodological benefits to the wide audience of IJMS. The issue will cover a broad area of serotonin as a biological substance, from distribution to functions, in the course of development, growth, and aging. Any subtleties of serotonin action in health and disease that you have uncovered using model systems in vertebrates and invertebrates are welcome!

Dr. Elena E. Voronezhskaya
Guest Editor

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Keywords

components of serotonergic system
serotonin targets
related systems
serotonergic mechanisms
experimental models

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Published Papers (6 papers)

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Research

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24 pages, 4007 KiB

Open AccessArticle

Parental Serotonin Modulation Alters Monoamine Balance in Identified Neurons and Affects Locomotor Activity in Progeny of Lymnaea stagnalis (Mollusca: Gastropoda)

by Anastasiia Shestipalova, Viktoriya Nikishchenko, Anton Bogomolov and Elena E. Voronezhskaya

Int. J. Mol. Sci. 2025, 26(6), 2454; https://doi.org/10.3390/ijms26062454 - 10 Mar 2025

Viewed by 1913

Abstract

Monoamine neurotransmitters play a critical role in the development and function of the nervous system. In this study, we investigated the impact of parental serotonin (5-HT) modulation on the monoamine balance in the identified apical neurons of Lymnaea stagnalis embryos and its influence on embryonic locomotor activity. Using immunocytochemical and pharmacological approaches, we detected serotonin in the apical neurons of veliger-stage embryos, observing that the relative 5-HT level within these neurons varied with seasonal conditions. Pharmacological elevation of parental 5-HT levels significantly increased the relative 5-HT level in the oocytes and subsequently in the apical neurons of their offspring. Notably, while the relative dopamine (DA) levels in these neurons remained stable, the increase in the relative 5-HT level significantly enhanced the embryos’ rotational locomotion. The expression of tryptophan hydroxylase (TPH), a key enzyme in serotonin synthesis, is a prerequisite for the elevation of the relative 5-HT level in apical neurons and is detected as early as the gastrula stage. Importantly, neither a reduction of 5-HT in the maternal organism by chlorpromazine application nor its pharmacological elevation via serotonin precursor (5-HTP) application at the cleavage stage affected the monoamine balance in apical neurons. These findings provide novel insights into how the parental 5-HT level selectively alters the monoamine phenotype of the identified neurons, offering a model for studying environmentally induced neural plasticity in early development. Full article

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

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15 pages, 1364 KiB

Open AccessArticle

Prenatal Stress Modulates Placental and Fetal Serotonin Levels and Determines Behavior Patterns in Offspring of Mice

by Victoria Melnikova, Nadezhda Lifantseva, Svetlana Voronova and Nadezhda Bondarenko

Int. J. Mol. Sci. 2024, 25(24), 13565; https://doi.org/10.3390/ijms252413565 - 18 Dec 2024

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Abstract

Available evidence from animal studies suggests that placental serotonin plays an important role in proper fetal development and programming by altering brain circuit formation, which later translates into altered abnormal adult behaviors. Several environmental stimuli, including stress and maternal inflammation, affect placental and, hence, fetal serotonin levels and thus may disturb fetal brain development. We investigated the effect of prenatal stress of varying intensities on the formation of adaptive behaviors in mouse offspring and the role of placental serotonin in these processes. Mild prenatal stress increased placental serotonin synthesis, whereas exposure to moderate stress decreased it. Prenatal stress of varying intensities also resulted in multidirectional changes in animal behavior in progeny, consistent with changes in serotonin levels in the placenta and fetal tissues. Mice exposed to mild prenatal stress showed higher sociality and exploratory activity, whereas, after moderate stress, in contrast, they avoided contact with other individuals of their species and had reduced exploratory activity, with no effect on locomotor activity. Thus, in mice, stressors of varying intensities during the critical period of intrauterine development can affect the synthesis of serotonin by the placenta and lead to multidirectional changes in animal behavior in postnatal life. Full article

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

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11 pages, 2678 KiB

Open AccessArticle

The Placenta as the Main Source of Serotonin in Ontogenetic Dynamics: Inflammation-Induced Modulation of Placental Serotonin Can Be Prevented by Immunoglobulin Administration

by Nadezhda Bondarenko, Nadezhda Lifantseva, Svetlana Voronova and Victoria Melnikova

Int. J. Mol. Sci. 2024, 25(24), 13532; https://doi.org/10.3390/ijms252413532 - 18 Dec 2024

Viewed by 845

Abstract

Placental serotonin is recognized as a key component of feto-placental physiology and can be influenced by environmental factors such as maternal diet, drugs, stress, and immune activation. In this study, we compared the contribution of placental and fetal sources to the maintenance of serotonin levels required for normal fetal development during ontogenetic dynamics. Our results demonstrated the leading role of the placenta at almost all stages of development. We investigated the modulatory effect of inflammation on placental serotonin levels. The data obtained showed that the susceptibility to prenatal inflammation depends on its severity and varies considerably at different stages of development. According to our results, inflammation-induced modulation of placental serotonin levels can be prevented by immunoglobulin administration at both early and late stages of development. Disturbances in placental serotonin signaling during critical developmental periods may have long-lasting consequences for the health and behavior of the offspring. Therefore, the ability to prevent environmental modulation of placental serotonin, and hence negative effects on the developing fetus, is of great importance. Full article

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

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18 pages, 10856 KiB

Open AccessArticle

Serotonin Signaling in Mouse Preimplantation Development: Insights from Transcriptomic and Structural-Functional Analyses

by Veronika S. Frolova, Yulia O. Nikishina, Yuri B. Shmukler and Denis A. Nikishin

Int. J. Mol. Sci. 2024, 25(23), 12954; https://doi.org/10.3390/ijms252312954 - 2 Dec 2024

Cited by 1 | Viewed by 1288

Abstract

Serotonin (5-HT), a versatile signaling molecule, plays a variety of roles in both neurotransmission and tissue regulation. The influence of serotonin on early development was first studied in marine invertebrate embryos and has since been documented in a variety of vertebrate species, including mammals. The present study investigates the expression and functional activity of serotonin components in mouse embryos, focusing on key receptors and transporters. Transcriptomic analyses revealed that mRNA transcripts related to serotonin show marked expression during the oogenesis and preimplantation stages. The results of the immunohistochemical studies show the presence of serotonin, the vesicular monoamine transporter VMAT2, and several membrane receptors (5-HT_1B, 5-HT_1D, 5-HT_2B, 5-HT₇) in the early stages of development. A functional analysis performed with the VMAT inhibitor reserpine revealed the crucial role of vesicular transport in the maintenance of serotonin signaling. The findings presented here support the hypothesis that serotonin plays a significant role in oocyte maturation and embryonic development, as well as in interblastomere interactions. Full article

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

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10 pages, 1811 KiB

Open AccessCommunication

Serotonin Transporter Activity in Mouse Oocytes Is a Positive Indicator of Follicular Growth and Oocyte Maturity

by Nina M. Alyoshina, Maria D. Tkachenko, Yulia O. Nikishina and Denis A. Nikishin

Int. J. Mol. Sci. 2023, 24(14), 11247; https://doi.org/10.3390/ijms241411247 - 8 Jul 2023

Cited by 4 | Viewed by 2403

Abstract

Serotonin (5-hydroxytryptamine, 5-HT) is known to be a regulator of oocyte maturation in a large number of animal species. In maturing mammalian oocytes, the accumulation of exogenous, maternal serotonin occurs due to the activity of the membrane transporter SERT. In this work, we investigated how SERT activity in oocytes correlates with indicators of follicular selection and oocyte maturity. An immunohistochemical study showed that the difference in the 5-HT intake activity in oocytes does not correlate with the marker of apoptosis in follicular cells, but positively correlates with markers of follicular growth, such as granulosa proliferation and follicle size. Functional analysis of oocytes at different stages of maturation showed that the expression and activity of SERT increases with oocyte maturation. An in vivo experiment on administration of the selective serotonin reuptake inhibitor fluoxetine (20 mg/kg) for 7 days showed a significant decrease in the content of serotonin in both growing GV-oocytes and ovulated mature MII-oocytes. The data obtained clearly indicate that the mechanism of specific membrane transport of serotonin normally ensures the accumulation of serotonin in maturing oocytes, and can be considered as a promising positive marker of their mature status. Full article

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

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Review

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15 pages, 699 KiB

Open AccessReview

The Serotonin 4 Receptor Subtype: A Target of Particular Interest, Especially for Brain Disorders

by Véronique Sgambato

Int. J. Mol. Sci. 2024, 25(10), 5245; https://doi.org/10.3390/ijms25105245 - 11 May 2024

Cited by 6 | Viewed by 2121

Abstract

In recent years, particular attention has been paid to the serotonin 4 receptor, which is well expressed in the brain, but also peripherally in various organs. The cerebral distribution of this receptor is well conserved across species, with high densities in the basal ganglia, where they are expressed by GABAergic neurons. The 5-HT₄ receptor is also present in the cerebral cortex, hippocampus, and amygdala, where they are carried by glutamatergic or cholinergic neurons. Outside the central nervous system, the 5-HT₄ receptor is notably expressed in the gastrointestinal tract. The wide distribution of the 5-HT₄ receptor undoubtedly contributes to its involvement in a plethora of functions. In addition, the modulation of this receptor influences the release of serotonin, but also the release of other neurotransmitters such as acetylcholine and dopamine. This is a considerable asset, as the modulation of the 5-HT₄ receptor can therefore play a direct or indirect beneficial role in various disorders. One of the main advantages of this receptor is that it mediates a much faster antidepressant and anxiolytic action than classical selective serotonin reuptake inhibitors. Another major benefit of the 5-HT₄ receptor is that its activation enhances cognitive performance, probably via the release of acetylcholine. The expression of the 5-HT₄ receptor is also altered in various eating disorders, and its activation by the 5-HT₄ agonist negatively regulates food intake. Additionally, although the cerebral expression of this receptor is modified in certain movement-related disorders, it is still yet to be determined whether this receptor plays a key role in their pathophysiology. Finally, there is no longer any need to demonstrate the value of 5-HT₄ receptor agonists in the pharmacological management of gastrointestinal disorders. Full article

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