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Neuromodulatory Effects of Serotonin
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Neuromodulatory Effects of Serotonin

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

Deadline for manuscript submissions: 25 July 2024 | Viewed by 4622

Special Issue Editor

Dr. Yasemin M. Akay

E-Mail Website
Guest Editor
Department of Biomedical Engineering, University of Houston, Houston, TX 77204-5060, USA
Interests: coronary artery disease; stent; noninvasive monitoring; nonlinear dynamics analysis; approximate entropy; 3D co-culture; glioblastoma; astrocytes; tumor microenvironment; PEGDA; addiction; cancer research; data science in medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Serotonin in the central nervous system has been recognized as an important neurotransmitter and neuromodulator which regulates various physiological functions, such as pain sensation, cognition, and emotions like fear, anxiety, and depression. Serotonin implements many complex functions in the body through its widespread and diverse receptors.

Current research activities have found the association of chronic pain and anxiety with synaptic plasticity in the anterior cingulate cortex and the spinal cord. Serotonin shows the multiple modulatory effects of synaptic transmission and plasticity in those structures, including activation, inhibition, and biphasic actions.

GBM, or glioblastoma multiforme, is a brain tumor which is often associated with epileptic seizures. Recent research suggests that neurotransmitters and neuromodulators such as Serotonin, found in the tumor microenvironment, affect the excitability, proliferation, quiescence, and differentiation of neurons, glial cells, and neural stem cells, playing a significant role in various stages of GBMs.

This Special Issue aims to provide selected contributions on advances in the neuromodulatory effects of Serotonin.

Potential topics include, but are not limited to:

  • Large-scale neuromodulation of Serotonin receptor networks.
  • Effects of persistent inward currents on individual motor unit discharge patterns.
  • Effects of Serotonin on retinal inputs in the thalamus.
  • Control of complex adaptive dynamics in the brain.
  • Chronic pain and injury-related anxiety.
  • Peripheral nerve stimulation.
  • Transcranial direct-current stimulation in major depressive disorder.
  • Effects of serotonin on fear learning.
  • Distribution of subcortical neuromodulatory afferents.
  • Emotional memory processing during REM sleep.
  • Role of Serotonin in Glioblastoma Multiforme (GBM).

Dr. Yasemin M. Akay
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neuromodulation
  • Serotonin
  • pain research
  • cognition
  • emotions
  • depression
  • anxiety
  • GBM

Published Papers (4 papers)

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Research

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16 pages, 2485 KiB  
Article
Poor Decision Making and Sociability Impairment Following Central Serotonin Reduction in Inducible TPH2-Knockdown Rats
by Lucille Alonso, Polina Peeva, Tania Fernández-del Valle Alquicira, Narda Erdelyi, Ángel Gil Nolskog, Michael Bader, York Winter, Natalia Alenina and Marion Rivalan
Int. J. Mol. Sci. 2024, 25(9), 5003; https://doi.org/10.3390/ijms25095003 - 3 May 2024
Viewed by 461
Abstract
Serotonin is an essential neuromodulator for mental health and animals’ socio-cognitive abilities. However, we previously found that a constitutive depletion of central serotonin did not impair rat cognitive abilities in stand-alone tests. Here, we investigated how a mild and acute decrease in brain [...] Read more.
Serotonin is an essential neuromodulator for mental health and animals’ socio-cognitive abilities. However, we previously found that a constitutive depletion of central serotonin did not impair rat cognitive abilities in stand-alone tests. Here, we investigated how a mild and acute decrease in brain serotonin would affect rats’ cognitive abilities. Using a novel rat model of inducible serotonin depletion via the genetic knockdown of tryptophan hydroxylase 2 (TPH2), we achieved a 20% decrease in serotonin levels in the hypothalamus after three weeks of non-invasive oral doxycycline administration. Decision making, cognitive flexibility, and social recognition memory were tested in low-serotonin (Tph2-kd) and control rats. Our results showed that the Tph2-kd rats were more prone to choose disadvantageously in the long term (poor decision making) in the Rat Gambling Task and that only the low-serotonin poor decision makers were more sensitive to probabilistic discounting and had poorer social recognition memory than other low-serotonin and control individuals. Flexibility was unaffected by the acute brain serotonin reduction. Poor social recognition memory was the most central characteristic of the behavioral network of low-serotonin poor decision makers, suggesting a key role of social recognition in the expression of their profile. The acute decrease in brain serotonin appeared to specifically amplify the cognitive impairments of the subgroup of individuals also identified as poor decision makers in the population. This study highlights the great opportunity the Tph2-kd rat model offers to study inter-individual susceptibilities to develop cognitive impairment following mild variations of brain serotonin in otherwise healthy individuals. These transgenic and differential approaches together could be critical for the identification of translational markers and vulnerabilities in the development of mental disorders. Full article
(This article belongs to the Special Issue Neuromodulatory Effects of Serotonin)
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15 pages, 1558 KiB  
Article
Gene–Environment Interactions in Irrational Beliefs: The Roles of Childhood Adversity and Multiple Candidate Genes
by Adina Chiș, Lia-Ecaterina Oltean, Mirela Bîlc, Romana Vulturar, Radu Șoflău, Daniel David, Aurora Szentágotai-Tătar and Andrei C. Miu
Int. J. Mol. Sci. 2024, 25(8), 4206; https://doi.org/10.3390/ijms25084206 - 10 Apr 2024
Viewed by 560
Abstract
Cognitive behavioral therapy is based on the view that maladaptive thinking is the causal mechanism of mental disorders. While this view is supported by extensive evidence, very limited work has addressed the factors that contribute to the development of maladaptive thinking. The present [...] Read more.
Cognitive behavioral therapy is based on the view that maladaptive thinking is the causal mechanism of mental disorders. While this view is supported by extensive evidence, very limited work has addressed the factors that contribute to the development of maladaptive thinking. The present study aimed to uncover interactions between childhood maltreatment and multiple genetic differences in irrational beliefs. Childhood maltreatment and irrational beliefs were assessed using multiple self-report instruments in a sample of healthy volunteers (N = 452). Eighteen single-nucleotide polymorphisms were genotyped in six candidate genes related to neurotransmitter function (COMT; SLC6A4; OXTR), neurotrophic factors (BDNF), and the hypothalamic–pituitary–adrenal axis (NR3C1; CRHR1). Gene–environment interactions (G×E) were first explored in models that employed one measure of childhood maltreatment and one measure of irrational beliefs. These effects were then followed up in models in which either the childhood maltreatment measure, the irrational belief measure, or both were substituted by parallel measures. Consistent results across models indicated that childhood maltreatment was positively associated with irrational beliefs, and these relations were significantly influenced by COMT rs165774 and OXTR rs53576. These results remain preliminary until independent replication, but they represent the best available evidence to date on G×E in a fundamental mechanism of psychopathology. Full article
(This article belongs to the Special Issue Neuromodulatory Effects of Serotonin)
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22 pages, 6408 KiB  
Article
Investigating the Influence of Morphine and Cocaine on the Mesolimbic Pathway Using a Novel Microimaging Platform
by Austin Ganaway, Kousuke Tatsuta, Virgil Christian Garcia Castillo, Ryoma Okada, Yoshinori Sunaga, Yasumi Ohta, Jun Ohta, Masahiro Ohsawa, Metin Akay and Yasemin M. Akay
Int. J. Mol. Sci. 2023, 24(22), 16303; https://doi.org/10.3390/ijms242216303 - 14 Nov 2023
Cited by 1 | Viewed by 984
Abstract
Dopamine (DA)’s relationship with addiction is complex, and the related pathways in the mesocorticolimbic system are used to deliver DA, regulating both behavioral and perceptual actions. Specifically, the mesolimbic pathway connecting the ventral tegmental area (VTA) and the nucleus accumbens (NAc) is crucial [...] Read more.
Dopamine (DA)’s relationship with addiction is complex, and the related pathways in the mesocorticolimbic system are used to deliver DA, regulating both behavioral and perceptual actions. Specifically, the mesolimbic pathway connecting the ventral tegmental area (VTA) and the nucleus accumbens (NAc) is crucial in regulating memory, emotion, motivation, and behavior due to its responsibility to modulate dopamine. To better investigate the relationship between DA and addiction, more advanced mapping methods are necessary to monitor its production and propagation accurately and efficiently. In this study, we incorporate dLight1.2 adeno-associated virus (AAV) into our latest CMOS (complementary metal-oxide semiconductor) imaging platform to investigate the effects of two pharmacological substances, morphine and cocaine, in the NAc using adult mice. By implanting our self-fabricated CMOS imaging device into the deep brain, fluorescence imaging of the NAc using the dLight1.2 AAV allows for the visualization of DA molecules delivered from the VTA in real time. Our results suggest that changes in extracellular DA can be observed with this adapted system, showing potential for new applications and methods for approaching addiction studies. Additionally, we can identify the unique characteristic trend of DA release for both morphine and cocaine, further validating the underlying biochemical mechanisms used to modulate dopaminergic activation. Full article
(This article belongs to the Special Issue Neuromodulatory Effects of Serotonin)
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Review

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15 pages, 940 KiB  
Review
Revisiting the Role of Serotonin in Sleep-Disordered Breathing
by O Aung, Mateus R. Amorim, David Mendelowitz and Vsevolod Y. Polotsky
Int. J. Mol. Sci. 2024, 25(3), 1483; https://doi.org/10.3390/ijms25031483 - 25 Jan 2024
Cited by 1 | Viewed by 1880
Abstract
Serotonin or 5-hydroxytryptamine (5-HT) is a ubiquitous neuro-modulator–transmitter that acts in the central nervous system, playing a major role in the control of breathing and other physiological functions. The midbrain, pons, and medulla regions contain several serotonergic nuclei with distinct physiological roles, including [...] Read more.
Serotonin or 5-hydroxytryptamine (5-HT) is a ubiquitous neuro-modulator–transmitter that acts in the central nervous system, playing a major role in the control of breathing and other physiological functions. The midbrain, pons, and medulla regions contain several serotonergic nuclei with distinct physiological roles, including regulating the hypercapnic ventilatory response, upper airway patency, and sleep–wake states. Obesity is a major risk factor in the development of sleep-disordered breathing (SDB), such as obstructive sleep apnea (OSA), recurrent closure of the upper airway during sleep, and obesity hypoventilation syndrome (OHS), a condition characterized by daytime hypercapnia and hypoventilation during sleep. Approximately 936 million adults have OSA, and 32 million have OHS worldwide. 5-HT acts on 5-HT receptor subtypes that modulate neural control of breathing and upper airway patency. This article reviews the role of 5-HT in SDB and the current advances in 5-HT-targeted treatments for SDB. Full article
(This article belongs to the Special Issue Neuromodulatory Effects of Serotonin)
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