Dualistic Equilibrium in Neurotransmission and Beyond: Unraveling the Pathophysiology and Unlocking Novel Therapeutic Targets in Neuropsychiatric Disorders

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: 30 November 2024 | Viewed by 9373

Special Issue Editors


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Guest Editor
HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Szeged, Hungary
Interests: neurohormones; neuropeptides; tryptophan; kynurenine; psychiatry; neurology; depression; anxiety; dementia; pain; Alzheimer’s disease; cognition; antidepressant; translational research
Special Issues, Collections and Topics in MDPI journals

E-Mail Website1 Website2
Guest Editor
1. Department of Psychology, University of Turin, Turin, Italy
2. Center for Studies and Research in Cognitive Neuroscience, Department of Psychology, University of Bologna, Bologna, Italy
Interests: NIBS techniques; TMS; skin conductance; heart rate variability; fear conditioning; fear learning; learning; neuropsychology; prefrontal cortex; amygdala; hippocampus; anxiety; depression; working memory; PTSD; skin conductance responses; psychophysiology; error-related negativity; EEG; tDCS; Alzheimer’s disease; PIT; stress-related disorders; Parkinson’s disease; resilience; memory; neurologic patients; cognitive decisions; fMRI; translational and molecular psychiatry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nearly 30 years have passed since significant progress was made in our understanding of the intricate interplay between alpha7 nicotinic acetylcholine (nACh) receptors and N-methyl-D-aspartate (NMDA) receptors in maintaining a delicate balance of intracellular calcium levels, which are crucial for proper memory function. However, the fine tuning of memory function extends beyond the interaction of these receptors, and comprises the dynamic involvement of various neurotransmitters, including serotonin, dopamine, norepinephrine, gamma-aminobutyric acid, and endorphins, which influence not only memory but also a variety of behavioral domains, such as emotional valence (positive and negative), cognitive processes, social interactions, arousal/regulatory systems, and sensorimotor systems. Furthermore, these neurotransmitters not only play essential roles in intracellular calcium levels, but also in modulating neuronal activity, synaptic transmission, and plasticity, all of which have an impact on a range of behaviors. Alterations in these neurotransmitter systems are commonly observed in neurodegenerative and psychiatric disorders, as well as systemic disorders, leading to cognitive impairment, emotional disturbances, and altered social interactions. Understanding the complex interactions between neurotransmitters and their effects on behavior is crucial for unraveling the pathophysiology of various disorders and developing effective therapeutic strategies. Memantine, for instance, is a psychopharmacon that restores the equilibrium between excitatory and inhibitory neurotransmission by targeting both the NMDA and cholinergic nervous systems, thereby enhancing cognitive function and alleviating neurological disorder symptoms. Moreover, non-invasive brain stimulation (NIBS) therapies, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have the potential to modulate neurotransmission by targeting brain circuits selectively and influencing neuronal activity.

This Special Issue highlights state-of-the-art research on how neurotransmission interacts to cause neuropsychiatric symptoms and illuminates potential new therapeutic targets for illnesses including systemic diseases, neurologic diseases, and psychiatric disorders. We invite authors to contribute original research and comprehensive review articles focusing on, but not limited to, the following:

  • Etiology, pathogenesis, and progression mechanisms;
  • Early diagnosis, including biomarker, bio-imaging, biosensors, and neuroimaging;
  • Methodology;
  • Prophylactic, disease-modifying, and therapeutic strategies;
  • Novel drug discovery and development, naturally driven biomedicines, natural bioactive molecules, and vaccines;
  • Novel targets in systemic diseases: cardiovascular, vascular, hematology, oncology, neurology, orthopedics, dermatology, ophthalmology, and other peripheral systems;
  • Predictors of clinical treatment responses;
  • Preclinical in vitro models and animal models;
  • Bench-to-bedside and bedside-to-bench translational research;
  • Computational neuroscience and computational psychiatry;
  • NIBS, TMS, and tDCS.

Dr. Masaru Tanaka
Dr. Simone Battaglia
Guest Editors

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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • Alzheimer’s disease
  • Parkinson’s disease
  • cognitive dysfunction
  • multiple sclerosis
  • stroke
  • migraine
  • chronic pain
  • depressive disorder
  • bipolar disorder
  • post-traumatic stress disorder
  • anxiety disorder
  • schizophrenia
  • somatic symptom disorder
  • autism spectrum disorder
  • hyperactive attention deficit disorder
  • learning disabilities
  • brain injuries
  • comorbidity
  • brain plasticity
  • transcranial magnetic stimulation (TMS)
  • transcranial direct current stimulation (tDCS)

Published Papers (5 papers)

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Research

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17 pages, 1563 KiB  
Article
Beyond the Brain: Perinatal Exposure of Rats to Serotonin Enhancers Induces Long-Term Changes in the Jejunum and Liver
by Romana Gračan, Sofia Ana Blažević, Matea Brižić and Dubravka Hranilovic
Biomedicines 2024, 12(2), 357; https://doi.org/10.3390/biomedicines12020357 - 3 Feb 2024
Cited by 1 | Viewed by 1124
Abstract
Serotonin (5-hydroxytryptamine, 5HT) homeostasis is essential for many physiological processes in the central nervous system and peripheral tissues. Hyperserotonemia, a measurable sign of 5HT homeostasis disruption, can be caused by 5HT-directed treatment of psychiatric and gastrointestinal diseases. Its impact on the long-term balance [...] Read more.
Serotonin (5-hydroxytryptamine, 5HT) homeostasis is essential for many physiological processes in the central nervous system and peripheral tissues. Hyperserotonemia, a measurable sign of 5HT homeostasis disruption, can be caused by 5HT-directed treatment of psychiatric and gastrointestinal diseases. Its impact on the long-term balance and function of 5HT in the peripheral compartment remains unresolved and requires further research due to possible effects on human health. We explored the effects of perinatal 5HT imbalance on the peripheral organs responsible for serotonin metabolism—the jejunum, a synthesis site, and the liver, a catabolism site—in adult rats. Hyperserotonemia was induced by subchronic treatment with serotonin precursor 5-hydroxytryptophan (5HTP) or serotonin degradation inhibitor tranylcypromine (TCP). The jejunum and liver were collected on postnatal day 70 and analyzed histomorphometrically. Relative mRNA levels of 5HT-regulating proteins were determined using qRT-PCR. Compared to controls, 5HTP- and TCP-treated rats had a reduced number of 5HT-producing cells and expression of the 5HT-synthesising enzyme in the jejunum, and an increased expression of 5HT-transporter accompanied by karyomegaly in hepatocytes, with these differences being more pronounced in the TCP-treated animals. Here, we report that perinatal 5HT disbalance induced long-term cellular and molecular changes in organs regulating 5HT-metabolism, which may have a negative impact on 5HT availability and function in the periphery. Our rat model demonstrates a link between the developmental abnormalities of serotonin homeostasis and 5HT-related changes in adult life and may be suitable for exploring the neurobiological substrates of vulnerability to behavioral and metabolic disorders, as well as for modeling the adverse effects of the prenatal exposure to 5HT enhancers in the human population. Full article
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16 pages, 1304 KiB  
Article
Cannabinoid and Serotonergic Systems: Unraveling the Pathogenetic Mechanisms of Stress-Induced Analgesia
by Hristina Nocheva, Nikolay Stoynev, Vlayko Vodenicharov, Dimo Krastev, Nikolay Krastev and Milka Mileva
Biomedicines 2024, 12(1), 235; https://doi.org/10.3390/biomedicines12010235 - 19 Jan 2024
Viewed by 1245
Abstract
The perception of „stress” triggers many physiological and behavioral responses, collectively called the stress response. Such a complex process allows for coping with stress and also triggers severe pathology. Because of the multidirectional effect of stress on the body, multiple systems participate in [...] Read more.
The perception of „stress” triggers many physiological and behavioral responses, collectively called the stress response. Such a complex process allows for coping with stress and also triggers severe pathology. Because of the multidirectional effect of stress on the body, multiple systems participate in its pathogenesis, with the endogenous cannabinoid and the serotoninergic ones among them. These two systems also take part in the pain perception decrease, known as stress-induced analgesia (SIA), which can then be taken as an indirect indicator of the stress response. The aim of our study was to study the changes in cold SIA (c-SIA) resulting from the exogenous activation of cannabinoid receptor type 1 (CB1) and 5-hydroxytryptamine (5-HT, serotonin) receptor type 1A (5-HT1A). Various combinations of agonists and/or antagonists of CB1 and 5-HT1A, before or after 1 h of cold exposure, were applied, since we presumed that the exogenous activation of the receptors before the cold exposure would influence the pathogenesis of the stress response, while their activation after the stressful trigger would influence the later development. Our results show that the serotonergic system “maintained” c-SIA in the pre-stress treatment, while the cannabinoids’ modulative effect was more prominent in the post-stress treatment. Here, we show the interactions of the two systems in the stress response. The interpretation and understanding of the mechanisms of interaction between CB1 and 5-HT1A may provide information for the prevention and control of adverse stress effects, as well as suggest interesting directions for the development of targeted interventions for the control of specific body responses. Full article
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18 pages, 3877 KiB  
Article
Unraveling the Role of miR-200b-3p in Attention-Deficit/Hyperactivity Disorder (ADHD) and Its Therapeutic Potential in Spontaneously Hypertensive Rats (SHR)
by Tung-Ming Chang, Hsiu-Ling Lin, Chih-Chen Tzang, Ju-An Liang, Tsai-Ching Hsu and Bor-Show Tzang
Biomedicines 2024, 12(1), 144; https://doi.org/10.3390/biomedicines12010144 - 10 Jan 2024
Viewed by 1252
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder in children with unknown etiology. Impaired learning ability was commonly reported in ADHD patients and has been associated with dopamine uptake in the striatum of an animal model. Another evidence also indicated that micro-RNA (miR)-200b-3p [...] Read more.
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder in children with unknown etiology. Impaired learning ability was commonly reported in ADHD patients and has been associated with dopamine uptake in the striatum of an animal model. Another evidence also indicated that micro-RNA (miR)-200b-3p is associated with learning ability in various animal models. However, the association between miR-200b-3p and ADHD–related symptoms remains unclear. Therefore, the current study investigated the role of miR-200b-3p in ADHD-related symptoms such as inattention and striatal inflammatory cytokines. To verify the influence of miR-200b-3p in ADHD-related symptoms, striatal stereotaxic injection of miR-200b-3p antagomir (AT) was performed on spontaneously hypertensive rats (SHR). The antioxidant activity and expressions of miR-200b-3p, slit guidance ligand 2 (Slit2), and inflammatory cytokines in the striatum of SHR were measured using quantitative real-time polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC), immunoblotting, and enzyme-linked immunosorbent assay (ELISA). The spontaneous alternation of SHR was tested using a three-arm Y-shaped maze. The administration of miR-200b-3p AT or taurine significantly decreased striatal tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in SHR, along with increased super-oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and significantly higher spontaneous alternation. In this paper, we show that miR-200b-3p AT and taurine alleviates ADHD-related symptoms in SHR. These findings provide insights into ADHD’s molecular basis and suggest miR-200b-3p as a potential therapeutic target. Concurrently, this study also suggests broad implications for treating neurodevelopmental disorders affecting learning activity such as ADHD. Full article
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Review

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24 pages, 1103 KiB  
Review
Evaluating p-tau217 and p-tau231 as Biomarkers for Early Diagnosis and Differentiation of Alzheimer’s Disease: A Narrative Review
by Dorian Julian Jarek, Hubert Mizerka, Jarosław Nuszkiewicz and Karolina Szewczyk-Golec
Biomedicines 2024, 12(4), 786; https://doi.org/10.3390/biomedicines12040786 - 3 Apr 2024
Viewed by 1360
Abstract
The escalating prevalence of Alzheimer’s disease (AD) highlights the urgent need to develop reliable biomarkers for early diagnosis and intervention. AD is characterized by the pathological accumulation of amyloid-beta plaques and tau neurofibrillary tangles. Phosphorylated tau (p-tau) proteins, particularly p-tau217 and p-tau231, have [...] Read more.
The escalating prevalence of Alzheimer’s disease (AD) highlights the urgent need to develop reliable biomarkers for early diagnosis and intervention. AD is characterized by the pathological accumulation of amyloid-beta plaques and tau neurofibrillary tangles. Phosphorylated tau (p-tau) proteins, particularly p-tau217 and p-tau231, have been identified as promising biomarker candidates to differentiate the disease progression from preclinical stages. This narrative review is devoted to a critical evaluation of the diagnostic accuracy, sensitivity, and specificity of p-tau217 and p-tau231 levels in the detection of AD, measured in plasma, serum, and cerebrospinal fluid, compared to established biomarkers. Additionally, the efficacy of these markers in distinguishing AD from other neurodegenerative disorders is examined. The significant advances offered by p-tau217 and p-tau231 in AD diagnostics are highlighted, demonstrating their unique utility in early detection and differential diagnosis. This comprehensive analysis not only confirms the excellent diagnostic capabilities of these markers, but also deepens the understanding of the molecular dynamics of AD, contributing to the broader scientific discourse on neurodegenerative diseases. This review is aimed to provide key information for researchers and clinicians across disciplines, filling interdisciplinary gaps and highlighting the role of p-tau proteins in revolutionizing AD research and clinical practice. Full article
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25 pages, 1046 KiB  
Review
The Orexin/Hypocretin System, the Peptidergic Regulator of Vigilance, Orchestrates Adaptation to Stress
by Miklós Jászberényi, Balázs Thurzó, Zsolt Bagosi, László Vécsei and Masaru Tanaka
Biomedicines 2024, 12(2), 448; https://doi.org/10.3390/biomedicines12020448 - 17 Feb 2024
Cited by 5 | Viewed by 2911
Abstract
The orexin/hypocretin neuropeptide family has emerged as a focal point of neuroscientific research following the discovery that this family plays a crucial role in a variety of physiological and behavioral processes. These neuropeptides serve as powerful neuromodulators, intricately shaping autonomic, endocrine, and behavioral [...] Read more.
The orexin/hypocretin neuropeptide family has emerged as a focal point of neuroscientific research following the discovery that this family plays a crucial role in a variety of physiological and behavioral processes. These neuropeptides serve as powerful neuromodulators, intricately shaping autonomic, endocrine, and behavioral responses across species. Notably, they serve as master regulators of vigilance and stress responses; however, their roles in food intake, metabolism, and thermoregulation appear complementary and warrant further investigation. This narrative review provides a journey through the evolution of our understanding of the orexin system, from its initial discovery to the promising progress made in developing orexin derivatives. It goes beyond conventional boundaries, striving to synthesize the multifaceted activities of orexins. Special emphasis is placed on domains such as stress response, fear, anxiety, and learning, in which the authors have contributed to the literature with original publications. This paper also overviews the advancement of orexin pharmacology, which has already yielded some promising successes, particularly in the treatment of sleep disorders. Full article
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