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Special Issue "Glutamate Receptors in Health and Disease II"

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: 31 January 2021.

Special Issue Editors

Assist. Prof. Joanna Wierońska
Website
Guest Editor
Department of Neurobiology, Institute of Pharmacology, Smętna Str. 12, 31‐343 Kraków, Poland
Interests: schizophrenia; metabotropic glutamate receptors; animal models; psychiatric disorders; serotonine
Special Issues and Collections in MDPI journals
Dr. Paulina Cieslik
Website
Guest Editor
Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Poland
Interests: schizophrenia; metabotropic glutamate receptors; animal models; psychiatric disorders; serotonine
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Glutamate constitutes the most abundant neurotransmitter in the vertebrate nervous system and influences the majority of processes in health and disease. In the human brain, almost 90% of the synaptic connections involve glutamate. Glutamate plays a pivotal role in synaptic plasticity and learning and memory processes and regulates growth cones and synaptogenesis during brain development. Excessive glutamate release and subsequent excitotoxicity occurs in ischemic cascade, stroke, and seizures. Disturbed glutamatergic neurotransmission may contribute to autism, some forms of intellectual disability, depression, schizophrenia, and diseases such as amyotrophic lateral sclerosis, lathyrism, and Alzheimer's disease.

Glutamate activity is regulated by a variety of receptors, including AMPA, NMDA, KA, and metabotropic glutamate receptors (mGlu). The AMPA, NMDA, and KA receptors are ionotropic receptors specialized for fast excitation, while metabotropic receptors act through second messenger systems to create slow, sustained effects. Glutamate excess is rapidly removed from the extracellular space by glutamatergic transporters (EAAT and VGLUT) that are located both in neurons and astrocytes.

All glutamatergic receptors were shown in neuroscience drug discovery studies to be excellent drug targets. Due to their pharmacological properties and localization, the mGlu receptors are especially important and promising.

This Special Issue, “Glutamate Receptors in Health and Disease”, aims to provide a summary of the field, to explore recent advances in the role of glutamate receptors in brain development and functioning, and to discuss how can we use pharmacological tools to regulate glutamatergic neurotransmissions in mental and neurodegenerative disorders. We invite authors to submit original research and review articles related to any of these aspects.

Assist. Prof. Joanna Wierońska
Dr. Paulina Cieslik
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 papers will be 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

  • glutamate;
  • metabotropic glutamate receptors;
  • ionotropic glutamate receptors;
  • psychiatric disorders;
  • neurodegeneration;
  • synaptic plasticity;
  • brain development;
  • glutamate transporters.

Related Special Issue

Published Papers (3 papers)

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Research

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Open AccessArticle
Density of GABAB Receptors Is Reduced in Granule Cells of the Hippocampus in a Mouse Model of Alzheimer’s Disease
Int. J. Mol. Sci. 2020, 21(7), 2459; https://doi.org/10.3390/ijms21072459 - 02 Apr 2020
Abstract
Metabotropic γ-aminobutyric acid (GABAB) receptors contribute to the control of network activity and information processing in hippocampal circuits by regulating neuronal excitability and synaptic transmission. The dysfunction in the dentate gyrus (DG) has been implicated in Alzheimer´s disease (AD). Given the [...] Read more.
Metabotropic γ-aminobutyric acid (GABAB) receptors contribute to the control of network activity and information processing in hippocampal circuits by regulating neuronal excitability and synaptic transmission. The dysfunction in the dentate gyrus (DG) has been implicated in Alzheimer´s disease (AD). Given the involvement of GABAB receptors in AD, to determine their subcellular localisation and possible alteration in granule cells of the DG in a mouse model of AD at 12 months of age, we used high-resolution immunoelectron microscopic analysis. Immunohistochemistry at the light microscopic level showed that the regional and cellular expression pattern of GABAB1 was similar in an AD model mouse expressing mutated human amyloid precursor protein and presenilin1 (APP/PS1) and in age-matched wild type mice. High-resolution immunoelectron microscopy revealed a distance-dependent gradient of immunolabelling for GABAB receptors, increasing from proximal to distal dendrites in both wild type and APP/PS1 mice. However, the overall density of GABAB receptors at the neuronal surface of these postsynaptic compartments of granule cells was significantly reduced in APP/PS1 mice. Parallel to this reduction in surface receptors, we found a significant increase in GABAB1 at cytoplasmic sites. GABAB receptors were also detected at presynaptic sites in the molecular layer of the DG. We also found a decrease in plasma membrane GABAB receptors in axon terminals contacting dendritic spines of granule cells, which was more pronounced in the outer than in the inner molecular layer. Altogether, our data showing post- and presynaptic reduction in surface GABAB receptors in the DG suggest the alteration of the GABAB-mediated modulation of excitability and synaptic transmission in granule cells, which may contribute to the cognitive dysfunctions in the APP/PS1 model of AD. Full article
(This article belongs to the Special Issue Glutamate Receptors in Health and Disease II)
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Review

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Open AccessReview
Regulation of Glutamatergic Activity via Bidirectional Activation of Two Select Receptors as a Novel Approach in Antipsychotic Drug Discovery
Int. J. Mol. Sci. 2020, 21(22), 8811; https://doi.org/10.3390/ijms21228811 - 20 Nov 2020
Abstract
Schizophrenia is a mental disorder that affects approximately 1–2% of the population and develops in early adulthood. The disease is characterized by positive, negative, and cognitive symptoms. A large percentage of patients with schizophrenia have a treatment-resistant disease, and the risk of developing [...] Read more.
Schizophrenia is a mental disorder that affects approximately 1–2% of the population and develops in early adulthood. The disease is characterized by positive, negative, and cognitive symptoms. A large percentage of patients with schizophrenia have a treatment-resistant disease, and the risk of developing adverse effects is high. Many researchers have attempted to introduce new antipsychotic drugs to the clinic, but most of these treatments failed, and the diversity of schizophrenic symptoms is one of the causes of disappointing results. The present review summarizes the results of our latest papers, showing that the simultaneous activation of two receptors with sub-effective doses of their ligands induces similar effects as the highest dose of each compound alone. The treatments were focused on inhibiting the increased glutamate release responsible for schizophrenia arousal, without interacting with dopamine (D2) receptors. Ligands activating metabotropic receptors for glutamate, GABAB or muscarinic receptors were used, and the compounds were administered in several different combinations. Some combinations reversed all schizophrenia-related deficits in animal models, but others were active only in select models of schizophrenia symptoms (i.e., cognitive or negative symptoms). Full article
(This article belongs to the Special Issue Glutamate Receptors in Health and Disease II)
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Open AccessReview
The Role of the N-Methyl-D-Aspartate Receptors in Social Behavior in Rodents
Int. J. Mol. Sci. 2019, 20(22), 5599; https://doi.org/10.3390/ijms20225599 - 09 Nov 2019
Cited by 2
Abstract
The appropriate display of social behaviors is essential for the well-being, reproductive success and survival of an individual. Deficits in social behavior are associated with impaired N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission. In this review, we describe recent studies using genetically modified mice and pharmacological [...] Read more.
The appropriate display of social behaviors is essential for the well-being, reproductive success and survival of an individual. Deficits in social behavior are associated with impaired N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission. In this review, we describe recent studies using genetically modified mice and pharmacological approaches which link the impaired functioning of the NMDA receptors, especially of the receptor subunits GluN1, GluN2A and GluN2B, to abnormal social behavior. This abnormal social behavior is expressed as impaired social interaction and communication, deficits in social memory, deficits in sexual and maternal behavior, as well as abnormal or heightened aggression. We also describe the positive effects of pharmacological stimulation of the NMDA receptors on these social deficits. Indeed, pharmacological stimulation of the glycine-binding site either by direct stimulation or by elevating the synaptic glycine levels represents a promising strategy for the normalization of genetically-induced, pharmacologically-induced or innate deficits in social behavior. We emphasize on the importance of future studies investigating the role of subunit-selective NMDA receptor ligands on different types of social behavior to provide a better understanding of the underlying mechanisms, which might support the development of selective tools for the optimized treatment of disorders associated with social deficits. Full article
(This article belongs to the Special Issue Glutamate Receptors in Health and Disease II)
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