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Biomedicines
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Glutamate Receptor in Health and Development
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Glutamate Receptor in Health and Development

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 20699

Special Issue Editor

Dr. Chin-Wei Huang

E-Mail Website
Guest Editor
Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
Interests: epilepsy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Glutamate is an essential excitatory neurotransmitter in the central nervous system that is involved indispensably in neuronal development and memory formation. Glutamate receptors, which mediate major excitatory synaptic transmission, regulate a wide spectrum of biological processes in normal development and health. The dysregulation of glutamate receptors and the glutamatergic system is involved in numerous neurological and psychiatric disorders. There are two main classes of glutamate receptors, ionotropic and metabotropic (mGluRs) receptors. The former stimulate fast excitatory neurotransmission and include N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid (AMPA), and kainite; while the latter are G protein-coupled receptors mediating glutamatergic activity via intracellular messenger systems. The ionotropic receptors play important roles, such as in synaptic plasticity in learning and memory or altered neuronal excitability in epileptic disorders, Parkinson’s disease, or Alzheimer’s disease. The mGluRs, categorized into three groups based on their signal transduction pathways and pharmacological profiles (Group I, II and III), are also involved in various psychiatric and neurological disorders, including mood disorders, Parkinson’s disease, Alzheimer’s disease, and chronic pain. Fundamental basic and translational clinical studies are actively required to determine the precise role of glutamate receptors in different neurological and psychiatric disorders. In this Special Issue, we wish to focus on a broad spectrum of basic and clinical studies on glutamate receptors in human development, health, and disease.

Dr. Chin-Wei Huang
Guest Editor

Manuscript Submission Information

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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.

Published Papers (5 papers)

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Research

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9 pages, 1042 KiB  
Communication
Effects of Transient Administration of the NMDA Receptor Antagonist MK-801 in Drosophila melanogaster Activity, Sleep, and Negative Geotaxis
by Thiago C. Moulin, Tijana Stojanovic, Rasika P. Rajesh, Tirusha Pareek, Laura Donzelli, Michael J. Williams and Helgi B. Schiöth
Biomedicines 2023, 11(1), 192; https://doi.org/10.3390/biomedicines11010192 - 12 Jan 2023
Cited by 3 | Viewed by 1845
Abstract
MK-801, also called dizocilpine, is an N-methyl-D-aspartate (NMDA) receptor antagonist widely used in animal research to model schizophrenia-like phenotypes. Although its effects in rodents are well characterised, little is known about the outcomes of this drug in other organisms. In this study, we [...] Read more.
MK-801, also called dizocilpine, is an N-methyl-D-aspartate (NMDA) receptor antagonist widely used in animal research to model schizophrenia-like phenotypes. Although its effects in rodents are well characterised, little is known about the outcomes of this drug in other organisms. In this study, we characterise the effects of MK-801 on the locomotion, sleep, and negative geotaxis of the fruit fly Drosophila melanogaster. We observed that acute (24 h) and chronic (7 days) administration of MK-801 enhanced negative geotaxis activity in the forced climbing assay for all tested concentrations (0.15 mM, 0.3 mM, and 0.6 mM). Moreover, acute administration, but not chronic, increased the flies’ locomotion in a dose-dependent matter. Finally, average sleep duration was not affected by any concentration or administration protocol. Our results indicate that acute MK-801 could be used to model hyperactivity phenotypes in Drosophila melanogaster. Overall, this study provides further evidence that the NMDA receptor system is functionally conserved in flies, suggesting the usefulness of this model to investigate several phenotypes as a complement and replacement of the rodent models within drug discovery. Full article
(This article belongs to the Special Issue Glutamate Receptor in Health and Development)
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Review

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16 pages, 1905 KiB  
Review
Pharmacological Potential of 3-Benzazepines in NMDAR-Linked Pathophysiological Processes
by Nadine Ritter, Paul Disse, Bernhard Wünsch, Guiscard Seebohm and Nathalie Strutz-Seebohm
Biomedicines 2023, 11(5), 1367; https://doi.org/10.3390/biomedicines11051367 - 5 May 2023
Cited by 2 | Viewed by 1647
Abstract
The number of N-Methyl-D-aspartate receptor (NMDAR) linked neurodegenerative diseases such as Alzheimer’s disease and dementia is constantly increasing. This is partly due to demographic change and presents new challenges to societies. To date, there are no effective treatment options. Current [...] Read more.
The number of N-Methyl-D-aspartate receptor (NMDAR) linked neurodegenerative diseases such as Alzheimer’s disease and dementia is constantly increasing. This is partly due to demographic change and presents new challenges to societies. To date, there are no effective treatment options. Current medications are nonselective and can lead to unwanted side effects in patients. A promising therapeutic approach is the targeted inhibition of NMDARs in the brain. NMDARs containing different subunits and splice variants display different physiological properties and play a crucial role in learning and memory, as well as in inflammatory or injury processes. They become overactivated during the course of the disease, leading to nerve cell death. Until now, there has been a lack of understanding of the general functions of the receptor and the mechanism of inhibition, which need to be understood in order to develop inhibitors. Ideal compounds should be highly targeted and even splice-variant-selective. However, a potent and splice-variant-selective NMDAR-targeting drug has yet to be developed. Recently developed 3-benzazepines are promising inhibitors for further drug development. The NMDAR splice variants GluN1-1b-4b carry a 21-amino-acid-long, flexible exon 5. Exon 5 lowers the NMDAR’s sensitivity to allosteric modulators by probably acting as an NMDAR modulator itself. The role of exon 5 in NMDAR modulation is still poorly understood. In this review, we summarize the structure and pharmacological relevance of tetrahydro-3-benzazepines. Full article
(This article belongs to the Special Issue Glutamate Receptor in Health and Development)
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21 pages, 1422 KiB  
Review
The Role of Glutamate Receptors in Epilepsy
by Tsang-Shan Chen, Tzu-Hsin Huang, Ming-Chi Lai and Chin-Wei Huang
Biomedicines 2023, 11(3), 783; https://doi.org/10.3390/biomedicines11030783 - 4 Mar 2023
Cited by 21 | Viewed by 7692
Abstract
Glutamate is an essential excitatory neurotransmitter in the central nervous system, playing an indispensable role in neuronal development and memory formation. The dysregulation of glutamate receptors and the glutamatergic system is involved in numerous neurological and psychiatric disorders, especially epilepsy. There are two [...] Read more.
Glutamate is an essential excitatory neurotransmitter in the central nervous system, playing an indispensable role in neuronal development and memory formation. The dysregulation of glutamate receptors and the glutamatergic system is involved in numerous neurological and psychiatric disorders, especially epilepsy. There are two main classes of glutamate receptor, namely ionotropic and metabotropic (mGluRs) receptors. The former stimulate fast excitatory neurotransmission, are N-methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and kainate; while the latter are G-protein-coupled receptors that mediate glutamatergic activity via intracellular messenger systems. Glutamate, glutamate receptors, and regulation of astrocytes are significantly involved in the pathogenesis of acute seizure and chronic epilepsy. Some glutamate receptor antagonists have been shown to be effective for the treatment of epilepsy, and research and clinical trials are ongoing. Full article
(This article belongs to the Special Issue Glutamate Receptor in Health and Development)
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17 pages, 1349 KiB  
Review
The Roles of Glutamate Receptors and Their Antagonists in Status Epilepticus, Refractory Status Epilepticus, and Super-Refractory Status Epilepticus
by Tzu-Hsin Huang, Ming-Chi Lai, Yu-Shiue Chen and Chin-Wei Huang
Biomedicines 2023, 11(3), 686; https://doi.org/10.3390/biomedicines11030686 - 23 Feb 2023
Cited by 2 | Viewed by 2455
Abstract
Status epilepticus (SE) is a neurological emergency with a high mortality rate. When compared to chronic epilepsy, it is distinguished by the durability of seizures and frequent resistance to benzodiazepine (BZD). The Receptor Trafficking Hypothesis, which suggests that the downregulation of γ-Aminobutyric acid [...] Read more.
Status epilepticus (SE) is a neurological emergency with a high mortality rate. When compared to chronic epilepsy, it is distinguished by the durability of seizures and frequent resistance to benzodiazepine (BZD). The Receptor Trafficking Hypothesis, which suggests that the downregulation of γ-Aminobutyric acid type A (GABAA) receptors, and upregulation of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors play major roles in the establishment of SE is the most widely accepted hypothesis underlying BZD resistance. NMDA and AMPA are ionotropic glutamate receptor families that have important excitatory roles in the central nervous system (CNS). They are both essential in maintaining the normal function of the brain and are involved in a variety of neuropsychiatric diseases, including epilepsy. Based on animal and human studies, antagonists of NMDA and AMPA receptors have a significant impact in ending SE; albeit most of them are not yet approved to be in clinically therapeutic guidelines, due to their psychomimetic adverse effects. Although there is still a dearth of randomized, prospective research, NMDA antagonists such as ketamine, magnesium sulfate, and the AMPA antagonist, perampanel, are regarded to be reasonable optional adjuvant therapies in controlling SE, refractory SE (RSE) or super-refractory SE (SRSE), though there are still a lack of randomized, prospective studies. This review seeks to summarize and update knowledge on the SE development hypothesis, as well as clinical trials using NMDA and AMPA antagonists in animal and human studies of SE investigations. Full article
(This article belongs to the Special Issue Glutamate Receptor in Health and Development)
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15 pages, 1269 KiB  
Review
Neurobiology of Depression: Chronic Stress Alters the Glutamatergic System in the Brain—Focusing on AMPA Receptor
by Ming Tatt Lee, Wei-Hao Peng, Hung-Wei Kan, Cheng-Chun Wu, Deng-Wu Wang and Yu-Cheng Ho
Biomedicines 2022, 10(5), 1005; https://doi.org/10.3390/biomedicines10051005 - 27 Apr 2022
Cited by 15 | Viewed by 6358
Abstract
Major depressive disorder (MDD) is a common neuropsychiatric disorder affecting the mood and mental well-being. Its pathophysiology remains elusive due to the complexity and heterogeneity of this disorder that affects millions of individuals worldwide. Chronic stress is frequently cited as the one of [...] Read more.
Major depressive disorder (MDD) is a common neuropsychiatric disorder affecting the mood and mental well-being. Its pathophysiology remains elusive due to the complexity and heterogeneity of this disorder that affects millions of individuals worldwide. Chronic stress is frequently cited as the one of the risk factors for MDD. To date, the conventional monoaminergic theory (serotonin, norepinephrine, and/or dopamine dysregulation) has received the most attention in the treatment of MDD, and all available classes of antidepressants target these monoaminergic systems. However, the contributions of other neurotransmitter systems in MDD have been widely reported. Emerging preclinical and clinical findings reveal that maladaptive glutamatergic neurotransmission might underlie the pathophysiology of MDD, thus revealing its critical role in the neurobiology of MDD and as the therapeutic target. Aiming beyond the monoaminergic hypothesis, studies of the neurobiological mechanisms underlying the stress-induced impairment of AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-glutamatergic neurotransmission in the brain could provide novel insights for the development of a new generation of antidepressants without the detrimental side effects. Here, the authors reviewed the recent literature focusing on the role of AMPA-glutamatergic neurotransmission in stress-induced maladaptive responses in emotional and mood-associated brain regions, including the hippocampus, amygdala, prefrontal cortex, nucleus accumbens and periaqueductal gray. Full article
(This article belongs to the Special Issue Glutamate Receptor in Health and Development)
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