Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Glutamate Receptors in Health and Disease

Special Issue Editors
Special Issue Information
Keywords
Related Special Issue
Published Papers

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

Deadline for manuscript submissions: closed (30 June 2019) | Viewed by 80598

Share This Special Issue

Special Issue Editors

Dr. Joanna Wierońska

E-Mail 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, Collections and Topics in MDPI journals

Dr. Paulina Cieslik

E-Mail 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, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Glutamate constitutes the most abundant neurotransmitter in the vertebrate nervous system and influences majority of processes in health and disease. In the human brain almost 90% of the synaptic connections involve glutamate. Glutamate plays pivotal role in synaptic plasticity, learning and memory processes, 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.

Activity of glutamate is regulated by variety of receptors, including AMPA, NMDA, KA and metabotropic glutamate receptors (mGlu). 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 extracellular space by glutamatergic transporters (EAAT and VGLUT) located both in neurons and in the astrocytes.

All glutamatergic receptors were shown to be excellent drug targets in neuroscience drug discovery. Due to pharmacological properties and localization, the family of mGlu receptors was shown to be 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 the glutamatergic neurotransmission 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 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

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

Related Special Issue

Glutamate Receptors in Health and Disease II in International Journal of Molecular Sciences (4 articles)

Published Papers (14 papers)

Download All Papers

Research

Jump to: Review

12 pages, 1867 KiB

Open AccessArticle

Kainate Receptor-Mediated Depression of Glutamate Release Involves Protein Kinase A in the Cerebellum

by Rafael Falcón-Moya, Pilar Losada-Ruiz and Antonio Rodríguez-Moreno

Int. J. Mol. Sci. 2019, 20(17), 4124; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20174124 - 23 Aug 2019

Cited by 11 | Viewed by 2444

Abstract

Kainate (KA) receptors (KAR) have important modulatory roles of synaptic transmission. In the cerebellum, the action mechanisms of KAR-mediated glutamatergic depression are unknown. We studied these mechanisms by recording evoked excitatory postsynaptic currents (eEPSCs) from cerebellar slices using the whole-cell configuration of the patch-clamp technique. We observed that 3 μM KA decreased the amplitude of eEPSCs and increased the number of failures at the synapses established between parallel fibers (PF) and Purkinje neurons, and the effect was antagonized by NBQX under the condition where AMPA receptors were previously blocked. The inhibition of protein kinase A (PKA) suppressed the effect of KAR activation on eEPSC, and effect was not prevented by protein kinase C inhibitors. Furthermore, in the presence of Pertussis toxin, the depression of glutamate release mediated by KAR activation was prevented, invoking the participation of a G_i/o protein in this modulation. Finally, the KAR-mediated depression of glutamate release was not prevented by blocking calcium-permeable KARs or by treatments that affect calcium release from intracellular stores. We conclude that KARs present at these synapses mediate an inhibition of glutamate release through a mechanism that involves the activation of G-protein and protein kinase A. Full article

(This article belongs to the Special Issue Glutamate Receptors in Health and Disease)

► Show Figures

Figure 1

12 pages, 1798 KiB

Open AccessArticle

Interleukin-10 Facilitates Glutamatergic Synaptic Transmission and Homeostatic Plasticity in Cultured Hippocampal Neurons

by Miroslav N. Nenov, Maxim V. Konakov, Ilia Y. Teplov and Sergey G. Levin

Int. J. Mol. Sci. 2019, 20(13), 3375; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20133375 - 09 Jul 2019

Cited by 16 | Viewed by 4271

Abstract

Anti-inflammatory cytokines are known to exert neuroprotective action ameliorating aberrant neuronal network activity associated with inflammatory responses. Yet, it is still not fully understood if anti-inflammatory cytokines play a significant role in the regulation of synaptic activity under normal conditions. Thus, the aim of our study was to investigate the effect of Interleukin-10 (IL-10) on neuronal synaptic transmission and plasticity. For this we tested the effect of IL-10 on miniature excitatory postsynaptic currents (mEPSC) and intracellular Ca²⁺ responses using whole-cell patch clamp and fluorescence microscopy in 13–15 DIV primary hippocampal neuroglial culture. We found that IL-10 significantly potentiated basal glutamatergic excitatory synaptic transmission within 15 min after application. Obtained results revealed a presynaptic nature of the effect, as IL-10 in a dose-dependent manner significantly increased the frequency but not the amplitude of mEPSC. Further, we tested the effect of IL-10 on mEPSC in a model of homeostatic synaptic plasticity (HSP) induced by treatment of primary hippocampal culture with 1 µM of tetrodotoxin (TTX) for a 24 h. It was found that 15 min application of IL-10 at established HSP resulted in enhanced mEPSC frequency, thus partially compensating for a decrease in the mEPSC frequency associated with TTX-induced HSP. Next, we studied if IL-10 can influence induction of HSP. We found that co-incubation of IL-10 with 1 µM of TTX for 24 h induced synaptic scaling, significantly increasing the amplitude of mEPSC and Ca²⁺ responses to application of the AMPA agonist, 5-Fluorowillardiine, thus facilitating a compensatory postsynaptic mechanism at HSP condition. Our results indicate that IL-10 potentiates synaptic activity in a dose- and time-dependent manner exerting both presynaptic (short-term exposure) and postsynaptic (long-term exposure) action. Obtained results demonstrate involvement of IL-10 in the regulation of basal glutamatergic synaptic transmission and plasticity at normal conditions. Full article

(This article belongs to the Special Issue Glutamate Receptors in Health and Disease)

► Show Figures

Figure 1

15 pages, 2190 KiB

Open AccessArticle

Acute and Chronic Sleep Deprivation-Related Changes in N-methyl-D-aspartate Receptor—Nitric Oxide Signalling in the Rat Cerebral Cortex with Reference to Aging and Brain Lateralization

by Zdenka Kristofikova, Jana Sirova, Jan Klaschka and Saak V. Ovsepian

Int. J. Mol. Sci. 2019, 20(13), 3273; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20133273 - 03 Jul 2019

Cited by 13 | Viewed by 3474

Abstract

Aging and chronic sleep deprivation (SD) are well-recognized risk factors for Alzheimer’s disease (AD), with N-methyl-D-aspartate receptor (NMDA) and downstream nitric oxide (NO) signalling implicated in the process. Herein, we investigate the impact of the age- and acute or chronic SD-dependent changes on the expression of NMDA receptor subunits (NR1, NR2A, and NR2B) and on the activities of NO synthase (NOS) isoforms in the cortex of Wistar rats, with reference to cerebral lateralization. In young adult controls, somewhat lateralized seasonal variations in neuronal and endothelial NOS have been observed. In aged rats, overall decreases in NR1, NR2A, and NR2B expression and reduction in neuronal and endothelial NOS activities were found. The age-dependent changes in NR1 and NR2B significantly correlated with neuronal NOS in both hemispheres. Changes evoked by chronic SD (dysfunction of endothelial NOS and the increasing role of NR2A) differed from those evoked by acute SD (increase in inducible NOS in the right side). Collectively, these results demonstrate age-dependent regulation of the level of NMDA receptor subunits and downstream NOS isoforms throughout the rat brain, which could be partly mimicked by SD. As described herein, age and SD alterations in the prevalence of NMDA receptors and NOS could contribute towards cognitive decline in the elderly, as well as in the pathobiology of AD and the neurodegenerative process. Full article

(This article belongs to the Special Issue Glutamate Receptors in Health and Disease)

► Show Figures

Figure 1

17 pages, 1928 KiB

Open AccessArticle

Reversal of MK-801-Induced Disruptions in Social Interactions and Working Memory with Simultaneous Administration of LY487379 and VU152100 in Mice

by Paulina Cieślik, Adrianna Radulska, Iwona Pelikant-Małecka, Agata Płoska, Leszek Kalinowski and Joanna M Wierońska

Int. J. Mol. Sci. 2019, 20(11), 2781; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20112781 - 06 Jun 2019

Cited by 14 | Viewed by 3261

Abstract

Negative and cognitive symptoms of schizophrenia contribute to an impaired social and professional life for schizophrenic patients, and in most cases, these symptoms are treatment resistant. Therefore, identification of new treatment strategies is sorely needed. Metabotropic glutamate receptors (mGlu) and muscarinic (M) receptors for acetylcholine have been considered promising targets for novel antipsychotics. Among them, mGlu₂ and M₄ subtypes seem to be of particular importance. In the present study, the effect of mutual activation of mGlu₂ and M₄ receptors was assessed in MK-801-based animal models of negative and cognitive symptoms of schizophrenia, that is, social interaction and novel object recognition tests. Low sub-effective doses of LY487379 (0.5 mg/kg), a positive allosteric activator of the mGlu₂ receptor, and VU152100 (0.25−0.5 mg/kg), a positive allosteric modulator of the M₄ receptor, were simultaneously administered in the aforementioned tests. Combined administration of these compounds prevented MK-801-induced disturbances in social interactions and object recognition when acutely administered 30 min before MK-801. Prolonged (7 days) administration of these compounds resulted in the loss of effectiveness in preventing MK-801-induced disruptions in the novel object recognition test but not in the social interaction test. In the next set of experiments, MK-801 (0.3 mg/kg) was administered for seven consecutive days, and the activity of the compounds was investigated on day eight, during which time MK-801 was not administered. In this model, based on prolonged MK-801 administration, the effectiveness of the compounds to treat MK-801-induced disruptions was evident at low doses which were ineffective in preventing the behavioural disturbances induced by an acute MK-801 injection. Combined administration of the compounds did not exert better efficacy than each compound given alone. Pharmacokinetic analysis confirmed a lack of possible drug–drug interactions after combined administration of LY487379 and VU152100. Our data show that modulation of M₄ and mGlu₂ receptors may potentially be beneficial in the treatment of negative and cognitive symptoms of schizophrenia. Full article

(This article belongs to the Special Issue Glutamate Receptors in Health and Disease)

► Show Figures

Figure 1

15 pages, 751 KiB

Open AccessArticle

Prophylactic Ketamine Treatment Promotes Resilience to Chronic Stress and Accelerates Recovery: Correlation with Changes in Synaptic Plasticity in the CA3 Subregion of the Hippocampus

by Adam Krzystyniak, Ewa Baczynska, Marta Magnowska, Svitlana Antoniuk, Matylda Roszkowska, Monika Zareba-Koziol, Nirmal Das, Subhadip Basu, Michal Pikula and Jakub Wlodarczyk

Int. J. Mol. Sci. 2019, 20(7), 1726; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20071726 - 08 Apr 2019

Cited by 32 | Viewed by 4931

Abstract

Ketamine is an N-methyl-d-aspartate receptor antagonist that has gained wide attention as a potent antidepressant. It has also been recently reported to have prophylactic effects in animal models of depression and anxiety. Alterations of neuroplasticity in different brain regions; such as the hippocampus; prefrontal cortex; and amygdala; are a hallmark of stress-related disorders; and such changes may endure beyond the treatment of symptoms. The present study investigated whether a prophylactic injection of ketamine has effects on structural plasticity in the brain in mice that are subjected to chronic unpredictable stress followed by an 8-day recovery period. Ketamine administration (3 mg/kg body weight) 1 h before stress exposure increased the number of resilient animals immediately after the cessation of stress exposure and positively influenced the recovery of susceptible animals to hedonic deficits. At the end of the recovery period; ketamine-treated animals exhibited significant differences in dendritic spine density and dendritic spine morphology in brain regions associated with depression compared with saline-treated animals. These results confirm previous findings of the prophylactic effects of ketamine and provide further evidence of an association between the antidepressant-like effect of ketamine and alterations of structural plasticity in the brain Full article

(This article belongs to the Special Issue Glutamate Receptors in Health and Disease)

► Show Figures

Graphical abstract

Review

Jump to: Research

25 pages, 1741 KiB

Open AccessReview

Deciphering GRINA/Lifeguard1: Nuclear Location, Ca²⁺ Homeostasis and Vesicle Transport

by Víctor Jiménez-González, Elena Ogalla-García, Meritxell García-Quintanilla and Albert García-Quintanilla

Int. J. Mol. Sci. 2019, 20(16), 4005; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20164005 - 16 Aug 2019

Cited by 10 | Viewed by 5074

Abstract

The Glutamate Receptor Ionotropic NMDA-Associated Protein 1 (GRINA) belongs to the Lifeguard family and is involved in calcium homeostasis, which governs key processes, such as cell survival or the release of neurotransmitters. GRINA is mainly associated with membranes of the endoplasmic reticulum, Golgi, endosome, and the cell surface, but its presence in the nucleus has not been explained yet. Here we dissect, with the help of different software tools, the potential roles of GRINA in the cell and how they may be altered in diseases, such as schizophrenia or celiac disease. We describe for the first time that the cytoplasmic N-terminal half of GRINA (which spans a Proline-rich domain) contains a potential DNA-binding sequence, in addition to cleavage target sites and probable PY-nuclear localization sequences, that may enable it to be released from the rest of the protein and enter the nucleus under suitable conditions, where it could participate in the transcription, alternative splicing, and mRNA export of a subset of genes likely involved in lipid and sterol synthesis, ribosome biogenesis, or cell cycle progression. To support these findings, we include additional evidence based on an exhaustive review of the literature and our preliminary data of the protein–protein interaction network of GRINA. Full article

(This article belongs to the Special Issue Glutamate Receptors in Health and Disease)

► Show Figures

Figure 1

39 pages, 860 KiB

Open AccessReview

Glial Cell AMPA Receptors in Nervous System Health, Injury and Disease

by Maria Ceprian and Daniel Fulton

Int. J. Mol. Sci. 2019, 20(10), 2450; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20102450 - 17 May 2019

Cited by 51 | Viewed by 6919

Abstract

Glia form a central component of the nervous system whose varied activities sustain an environment that is optimised for healthy development and neuronal function. Alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA)-type glutamate receptors (AMPAR) are a central mediator of glutamatergic excitatory synaptic transmission, yet they are also expressed in a wide range of glial cells where they influence a variety of important cellular functions. AMPAR enable glial cells to sense the activity of neighbouring axons and synapses, and as such many aspects of glial cell development and function are influenced by the activity of neural circuits. However, these AMPAR also render glia sensitive to elevations of the extracellular concentration of glutamate, which are associated with a broad range of pathological conditions. Excessive activation of AMPAR under these conditions may induce excitotoxic injury in glial cells, and trigger pathophysiological responses threatening other neural cells and amplifying ongoing disease processes. The aim of this review is to gather information on AMPAR function from across the broad diversity of glial cells, identify their contribution to pathophysiological processes, and highlight new areas of research whose progress may increase our understanding of nervous system dysfunction and disease. Full article

(This article belongs to the Special Issue Glutamate Receptors in Health and Disease)

► Show Figures

Figure 1

18 pages, 2248 KiB

Open AccessReview

STIM Proteins and Glutamate Receptors in Neurons: Role in Neuronal Physiology and Neurodegenerative Diseases

by Karolina Serwach and Joanna Gruszczynska-Biegala

Int. J. Mol. Sci. 2019, 20(9), 2289; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20092289 - 09 May 2019

Cited by 27 | Viewed by 6730

Abstract

Neuronal calcium (Ca²⁺) influx has long been ascribed mainly to voltage-gated Ca²⁺ channels and glutamate receptor channels. Recent research has shown that it is also complemented by stromal interaction molecule (STIM) protein-mediated store-operated Ca²⁺ entry (SOCE). SOCE is described as Ca²⁺ flow into cells in response to the depletion of endoplasmic reticulum Ca²⁺ stores. The present review summarizes recent studies that indicate a relationship between neuronal SOCE that is mediated by STIM1 and STIM2 proteins and glutamate receptors under both physiological and pathological conditions, such as neurodegenerative disorders. We present evidence that the dysregulation of neuronal SOCE and glutamate receptor activity are hallmarks of acute neurodegenerative diseases (e.g., traumatic brain injury and cerebral ischemia) and chronic neurodegenerative diseases (e.g., Alzheimer’s disease and Huntington’s disease). Emerging evidence indicates a role for STIM proteins and glutamate receptors in neuronal physiology and pathology, making them potential therapeutic targets. Full article

(This article belongs to the Special Issue Glutamate Receptors in Health and Disease)

► Show Figures

Figure 1

13 pages, 925 KiB

Open AccessReview

Glutamate Receptors and Glioblastoma Multiforme: An Old “Route” for New Perspectives

by Lorenzo Corsi, Andrea Mescola and Andrea Alessandrini

Int. J. Mol. Sci. 2019, 20(7), 1796; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20071796 - 11 Apr 2019

Cited by 40 | Viewed by 5875

Abstract

Glioblastoma multiforme (GBM) is the most aggressive malignant tumor of the central nervous system, with poor survival in both treated and untreated patients. Recent studies began to explain the molecular pathway, comprising the dynamic structural and mechanical changes involved in GBM. In this context, some studies showed that the human glioblastoma cells release high levels of glutamate, which regulates the proliferation and survival of neuronal progenitor cells. Considering that cancer cells possess properties in common with neural progenitor cells, it is likely that the functions of glutamate receptors may affect the growth of cancer cells and, therefore, open the road to new and more targeted therapies. Full article

(This article belongs to the Special Issue Glutamate Receptors in Health and Disease)

► Show Figures

Graphical abstract

37 pages, 1616 KiB

Open AccessReview

Glutamatergic Signaling Along The Microbiota-Gut-Brain Axis

by Andreina Baj, Elisabetta Moro, Michela Bistoletti, Viviana Orlandi, Francesca Crema and Cristina Giaroni

Int. J. Mol. Sci. 2019, 20(6), 1482; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20061482 - 25 Mar 2019

Cited by 171 | Viewed by 16225

Abstract

A complex bidirectional communication system exists between the gastrointestinal tract and the brain. Initially termed the “gut-brain axis” it is now renamed the “microbiota-gut-brain axis” considering the pivotal role of gut microbiota in maintaining local and systemic homeostasis. Different cellular and molecular pathways act along this axis and strong attention is paid to neuroactive molecules (neurotransmitters, i.e., noradrenaline, dopamine, serotonin, gamma aminobutyric acid and glutamate and metabolites, i.e., tryptophan metabolites), sustaining a possible interkingdom communication system between eukaryota and prokaryota. This review provides a description of the most up-to-date evidence on glutamate as a neurotransmitter/neuromodulator in this bidirectional communication axis. Modulation of glutamatergic receptor activity along the microbiota-gut-brain axis may influence gut (i.e., taste, visceral sensitivity and motility) and brain functions (stress response, mood and behavior) and alterations of glutamatergic transmission may participate to the pathogenesis of local and brain disorders. In this latter context, we will focus on two major gut disorders, such as irritable bowel syndrome and inflammatory bowel disease, both characterized by psychiatric co-morbidity. Research in this area opens the possibility to target glutamatergic neurotransmission, either pharmacologically or by the use of probiotics producing neuroactive molecules, as a therapeutic approach for the treatment of gastrointestinal and related psychiatric disorders. Full article

(This article belongs to the Special Issue Glutamate Receptors in Health and Disease)

► Show Figures

Figure 1

17 pages, 2873 KiB

Open AccessReview

NMDA Receptor Model of Antipsychotic Drug-Induced Hypofrontality

by Marek Krzystanek and Artur Pałasz

Int. J. Mol. Sci. 2019, 20(6), 1442; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20061442 - 21 Mar 2019

Cited by 18 | Viewed by 7661

Abstract

Schizophrenia is a chronic mental disease, affecting around 1% of the general population. Schizophrenia is characterized by productive, negative, affective, and disorganization symptoms, and cognitive deficits. Cognitive deficits prevail in most of the schizophrenia patients and are one of the most disabling symptoms. They usually occur before the acute episode of the disease and tend to become chronic with no satisfactory treatment from antipsychotic drugs. Because of their early manifestation in patients’ lives, cognitive deficits are suggested to be the primary symptom of schizophrenia. The pathogenesis of cognitive deficits in schizophrenia is not fully understood. They are linked with hypofrontality, which is a decrease in blood flow and glucose metabolism in the prefrontal lobe of schizophrenia-suffering patients. Hypofrontality is linked with disturbances of the corticolimbothalamic circuit, important for cognition and memory in humans. The circuit consists of a group of neuroanatomic structures and hypothetically any disturbance in them may result in cognitive deficits. We present a translational preclinical model of understanding how antipsychotic medication may decrease the N-methyl-D-aspartic acid (NMDA) receptors’ activity and produce dysfunctions in the corticolimbothalamic circuit and hypofrontality. From several pharmacological experiments on rats, including mainly our own recent findings, we collected data that suggest that antipsychotic medication may maintain and escalate hypofrontality in schizophrenia, decreasing NMDA receptor activity in the corticolimbothalamic circuit in the human brain. We discuss our findings within the literature of the subject. Full article

(This article belongs to the Special Issue Glutamate Receptors in Health and Disease)

► Show Figures

Graphical abstract

24 pages, 379 KiB

Open AccessReview

The Role of Metabotropic Glutamate Receptors in Social Behavior in Rodents

by Iulia Zoicas and Johannes Kornhuber

Int. J. Mol. Sci. 2019, 20(6), 1412; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20061412 - 20 Mar 2019

Cited by 28 | Viewed by 4373

Abstract

The appropriate display of social behavior is critical for the well-being and survival of an individual. In many psychiatric disorders, including social anxiety disorder, autism spectrum disorders, depression and schizophrenia social behavior is severely impaired. Selective targeting of metabotropic glutamate receptors (mGluRs) has emerged as a novel treatment strategy for these disorders. In this review, we describe some of the behavioral paradigms used to assess different types of social behavior, such as social interaction, social memory, aggressive behavior and sexual behavior. We then focus on the effects of pharmacological modulation of mGluR1-8 on these types of social behavior. Indeed, accumulating evidence indicates beneficial effects of selective ligands of specific mGluRs in ameliorating innate or pharmacologically-induced deficits in social interaction and social memory as well as in reducing aggression in rodents. We emphasize the importance of future studies investigating the role of selective mGluR ligands on different types of social behavior to provide a better understanding of the neural mechanisms involved which, in turn, might promote the development of selective mGluR-targeted tools for the improved treatment of psychiatric disorders associated with social deficits. Full article

(This article belongs to the Special Issue Glutamate Receptors in Health and Disease)

15 pages, 1022 KiB

Open AccessReview

Role of Serotonergic System in the Antidepressant Actions of mGlu2/3 Receptor Antagonists: Similarity to Ketamine

by Shigeyuki Chaki and Kenichi Fukumoto

Int. J. Mol. Sci. 2019, 20(6), 1270; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20061270 - 13 Mar 2019

Cited by 23 | Viewed by 4473

Abstract

Numerous studies have demonstrated the antidepressant effects of group II metabotropic glutamate (mGlu2/3) receptor antagonists in various rodent models. Importantly, it has been shown that the antidepressant effects of mGlu2/3 receptor antagonists in rodent models are similar to those of ketamine, which exerts rapid and long-lasting antidepressant effects in patients with major depressive disorders, including patients with treatment-resistant depression. In addition, the synaptic mechanisms underlying the effects of mGlu2/3 receptor antagonists are reported to be similar to those underlying the effects of ketamine. The roles of the serotonergic system in the antidepressant effects of mGlu2/3 receptor antagonists have recently been demonstrated. Moreover, it was investigated how mGlu2/3 receptor antagonists interact with the serotonergic system to exert antidepressant effects. Notably, the same neural mechanisms as those underlying the effects of ketamine may be involved in the antidepressant actions of the mGlu2/3 receptor antagonists. In this review, we shall summarize the antidepressant potential of mGlu2/3 receptor antagonists and their mechanisms of action in comparison with those of ketamine. In particular, we shall focus on the roles of the serotonergic system in the antidepressant actions of mGlu2/3 receptor antagonists. Full article

(This article belongs to the Special Issue Glutamate Receptors in Health and Disease)

► Show Figures

Figure 1

17 pages, 2358 KiB

Open AccessReview

The Reactive Plasticity of Hippocampal Ionotropic Glutamate Receptors in Animal Epilepsies

by András Mihály

Int. J. Mol. Sci. 2019, 20(5), 1030; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20051030 - 27 Feb 2019

Cited by 15 | Viewed by 3863

Abstract

Ionotropic glutamate receptors (iGluRs) mediate the synaptic and metabolic actions of glutamate. These iGluRs are classified within the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type, kainate-type, and N-methyl-d-aspartate (NMDA)-type functional receptor families. The iGluR assemblies are regulated by transcription, alternative splicing, and cytoplasmic post-translational modifications. The iGluR subunit proteins are transported from the endoplasmic reticulum, inserted into the synaptic membranes, and anchored at their action site by different scaffolding and interacting proteins. The functional properties of iGluRs depend on their subunit composition, the amino acid sequence of the protein domains, and the scaffolding proteins in the synaptic membranes. The iGluRs are removed from the membranes by enzymatic action and endocytosis. Hippocampal iGluRs are rearranged through the upregulation and downregulation of the subunits following deafferentation and epileptic seizures. The rearrangement of iGluRs and the alteration of their subunit composition transform neurons into “pathological” cells, determining the further plasticity or pathology of the hippocampal formation. In the present review, we summarize the expression of AMPA, kainate, and NMDA receptor subunits following deafferentation, repeated mild seizures, and status epilepticus. We compare our results to literature descriptions, and draw conclusions as to the reactive plasticity of iGluRs in the hippocampus. Full article

(This article belongs to the Special Issue Glutamate Receptors in Health and Disease)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Glutamate Receptors in Health and Disease

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Related Special Issue

Published Papers (14 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI